Serum Insulin Concentrations Research Articles

Betaine and B12 intake, glutathione concentration, and MTHFR, PEMT, and MTHFD1 genotypes are associated with diabetes-related parameters in Polish adults

BackgroundThere is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, DHFR (rs70991108) genotype, MTHFR (rs180113) genotype, MTHFD1 (rs2236225) genotype, PEMT (rs7946 and rs12325817) genotype with fasting glucose level insulin level, and diabetes related indices. MethodsThe study group consisted of 421 Polish adults aged 20–40 years old. Food intake was assessed using a three-day food diary. Plasma concentrations of choline, betaine, and TMAO were determined using ultra-high-performance liquid chromatography electrospray ionization mass spectrometry. Total plasma GSH level was measured using high-performance liquid chromatography. Insulin, folate and vitamin B12 concentrations were estimated using an enzyme-linked immunosorbent assay method. Genotyping was performed using TaqMan probes. ResultsGSH level was negatively associated with insulin (β = -0.11, p < 0.05) and gamma-glutamyltransferase (β = -0.12, p < 0.05), and positively associated with fasting glucose (β = 0.11, p < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = -0.13, p < 0.05) and HOMA-IR (β = -0.12, p < 0.05). Choline intake was negatively associated with insulin (β = -0.17, p < 0.01). Serum folate level was negatively associated with GGTP (β = -0.11; p < 0.05). The MTHFR CC genotype was associated with higher serum insulin level (β = 0.15; p < 0.01) and higher HOMA-IR (β = 0.15, p < 0.01), while the MTHFD1 AA genotype was negatively associated with QUICKI (β = -0.11, p < 0.05). ConclusionsOur findings suggest that higher GSHl higher intake of betaine, B12, and choline; as well as TT genotype of MTHFR and AA genotype of MTHFD1 are associated with lower diabetes-related parameters among adults.

PSIX-12 Influence of obesity on satiety hormones, serum metabolome, and fecal microbiome in adult dogs

Abstract The objective of this study was to investigate the difference between lean and obese dogs in terms of their satiety hormones, serum metabolome, and fecal microbiome. Mixed-breed lean (n = 30; 17 male and 13 female; 4.0 ± 2.5 yr of age; 24.6 ± 6.3% body fat) and obese (n = 30; 19 male and 11 female; 7.3 ± 2.1 yr of age; 46.9 ± 3.9% body fat) adult dogs were used in this study. Blood samples were collected to measure satiety hormones and serum metabolome, and fresh fecal samples were collected for microbiome analysis. It was hypothesized that obese dogs had altered metabolism and gut microbiome compared with lean dogs. Data were analyzed using MIXED procedure of SAS, using body type as the fixed effect and dog as the random effect. Results showed that obese dogs had greater (P &amp;lt; 0.05) serum leptin, insulin, and insulin-like growth factor-1 (IGF-1) concentrations, but reduced (P &amp;lt; 0.05) gastric inhibitory peptide (GIP) than lean dogs. Serum concentrations of all essential amino acids except for threonine in obese dogs were greater (P &amp;lt; 0.05) than in lean dogs. Obese dogs also had greater (P &amp;lt; 0.05) concentrations of serum N-Lactoyl amino acids and dipeptides except for prolylglycine than their lean counterparts. Additionally, concentrations of serum long-chain saturated and monounsaturated fatty acids were less (P &amp;lt; 0.05; only for myristate, pentadecanoate, and non-adecanoate) or similar in obese dogs compared with lean dogs. Serum oxidative stress makers, such as oxidized glutathione, cysteine-glutathione, and 4-hydroxynonenal, were greater (P &amp;lt; 0.05) in obese dogs than lean dogs. Furthermore, obese dogs had less (P &amp;lt; 0.05) fecal Firmicutes, but greater (P &amp;lt; 0.05) fecal Bacteroidetes and Fusobacteria, compared with lean dogs. There were no differences (P &amp;gt; 0.10) in fecal microbiome alpha diversity, such as Chao1 and Shannon index, between lean and obese dogs. In conclusion, obese dogs had differential body metabolism and gut microbiome compared with lean dogs.

Effect of inulin from dahlia tubers (Dahlia variabilis) extract on insulitis severity and insulin expression in diabetic rats.

Dahlia (Dahlia variabilis), a widely cultivated ornamental plant in Indonesia, is known to contain 84.08% inulin in its tubers. Numerous studies have demonstrated the antidiabetic potential of inulin from various plant sources. However, most of the research is in the form of a mixture of inulin with other active substances, and no one has analyzed the effects of inulin derived from dahlia tubers. This study examines the effect of inulin from dahlia tuber extract on blood glucose levels, serum insulin expression, pancreatic tissue insulin expression, homeostatic model assessment of insulin resistance (HOMA-IR), and the extent of insulitis in diabetic rats. In this experimental study, 20 male Wistar rats were randomly allocated to five groups. Group I served as the control, Group II as the STZ-induced diabetic group, Group III as the STZ-induced diabetic group treated with inulin (0.5 g/kgBW), Group IV as the STZ induced diabetic group treated with inulin (1.0 g/kgBW), and Group V as the STZ-induced diabetic group treated with inulin (1.5 g/kgBW). The inulin was administered for 21 days. The degree of insulitis was evaluated using a scoring system, serum insulin concentration via ELISA, and insulin expression in the pancreas through immunohistochemistry. Administration of inulin from dahlia tubers significantly reduced serum glucose concentrations in diabetic rats. Notably, only inulin extracts at doses of 1 g/kgBW and 1.5 g/kgBW showed a significant reduction in insulitis and HOMA-IR index in diabetic rats, while the 0.5 g/kgBW inulin extract reduced insulitis without affecting HOMA-IR. Inulin extract administration did not affect insulin expression in serum or pancreatic tissue. Inulin from dahlia tuber can exert antidiabetic properties by improving insulin resistance and insulitis. These studies suggest the great potential of dahlia tubers as the source of inulin for prebiotic functional foods.

Effects of High-Intensity Intermittent Training on Metabolic Parameters and Irisin Levels in High-Fat-Fed Rats

Objective: To investigate the effects of high-intensity intermittent training (HIIT) on preventing significant weight gain and provide scientific theoretical support and practical guidance for reducing the occurrence of obesity. Methods: Twenty-four Sprague-Dawley rats were randomly divided into four groups: the control sedentary group (CS), the high-fat sedentary group (HS), the high-fat continuous exercise group (HE), and the high-fat intermittent exercise group (HI). The HE and HI groups underwent five days of continuous low-intensity exercise and eight weeks of high-intensity intermittent exercise. Weekly monitoring included measurements of food intake and body weight. An automatic biochemical analyzer was used to assess blood lipid and glucose levels, while ELISA kits measured serum insulin and irisin content. H&amp;E staining was used to observe adipocyte size. Results: In the HS group, body weight, blood lipid levels, blood glucose levels, and adipocyte size significantly increased, while the QUICKI index decreased. In the HI group, body weight, blood lipid levels, blood glucose levels, and adipocyte size decreased, and the QUICKI index increased. The effects of high-intensity intermittent exercise were superior to those of continuous low-intensity exercise. In the HI group, serum irisin levels did not change significantly after exercise, while in the HE group, there was a slight upward trend in irisin levels. Conclusion: A high-fat diet induced abnormal metabolism in rats. HIIT effectively prevents metabolic abnormalities induced by a high-fat diet, and its effects are more pronounced than those of low-intensity exercise. HIIT stimulates the secretion of blood irisin, affecting secretion levels, and may represent a novel mechanism for maintaining metabolic homeostasis. This has important implications for controlling significant weight gain.

Replacing Cereal with Ultraprocessed Foods in Pig Diets Does Not Adverse Gut Microbiota, L-glutamate Uptake, or Serum Insulin

BackgroundUsing ultraprocessed food (UPF) to replace traditional feed ingredients offers a promising strategy for enhancing food production sustainability. ObjectiveTo analyze the impact of salty and sugary UPF on gut microbiota, amino acids uptake, and serum analytes in growing and finishing pig. MethodsThirty-six Swiss Large White male castrated pigs were assigned to 3 experimental diets: 1) standard (ST), 0% UPF; 2) 30% conventional ingredients replaced by sugary (SU) UPF; and 3) 30% conventional ingredients replaced by salty (SA) UPF. The next-generation sequencing was used to characterize the fecal microbiota. Transepithelial electrical resistance and the active uptake of selected amino acids in pig jejuna were also evaluated. Data were enriched with measurements of fecal volatile fatty acids and serum urea, minerals, and insulin. All data analyses were run in R v4.0.3. The packages phyloseq, vegan, microbiome, and microbiomeutilities were used for microbiota data analysis. The remaining data were analyzed by analysis of variance using linear mixed-effects regression models. ResultsThe UPF did not affect fecal microbiota abundance or biodiversity. The Firmicutes to Bacteroidetes ratio remained unaffected. SU-induced increase in the Anaerostipes genus suggested altered glucose metabolism, whereas SA increased the abundance of CAG-352 and p-2534-18B. No effects on fecal volatile fatty acids were observed. Assumptions of UPF negatively affecting small intestinal physiology were not supported by the measurements of transepithelial electrical resistance in pigs. Active amino acids uptake tests showed potential decrease in L-glutamate absorption in the SA compared with the SU diet. Blood serum analysis indicated no adverse effects on urea, calcium, magnesium, or potassium concentration but the SU group resulted in a lower blood serum insulin concentration at the time of blood collection. ConclusionsWhen incorporated at 30% into a standard growing finishing diet for pigs, UPF does not have detrimental effects on gut microbiota, intestinal integrity, and blood mineral homeostasis.

Metabolic characteristics of different phenotypes in reproductive-aged women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder in reproductive-aged women. The study was designed to investigate the metabolic characteristics of different phenotypes in women with PCOS of reproductive age. A total of 442 women with PCOS were recruited in this cross-sectional study. According to different phenotypes, all women were divided into three groups: the chronic ovulatory dysfunction and hyperandrogenism group (OD-HA group, n = 138), the chronic ovulatory dysfunction and polycystic ovarian morphology group (OD-PCOM group, n = 161), and the hyperandrogenism and polycystic ovarian morphology group (HA-PCOM group, n = 143). The metabolic risk factors and prevalence rates of metabolic disorders among the three groups were compared. The body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) of women from the OD-HA group and HA-PCOM group were significantly higher than those of women from the OD-PCOM group (p < 0.05). The serum insulin concentration and homeostasis model assessment of insulin resistance (HOMA IR) at 2h and 3h after oral glucose powder in women from the OD-HA group and HA-PCOM group were significantly higher than those from the OD-PCOM group (p < 0.05). The serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in women from the OD-HA group and HA-PCOM group were significantly higher than those in women from the OD-PCOM group (p < 0.05). The prevalence rates of impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), insulin resistance (IR), metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and dyslipidemia of women with PCOS were 17.9%, 3.6%, 58.4%, 29.4%, 46.6%, and 43.4%, respectively. The prevalence rates of IGT, IR, MS, NAFLD, and dyslipidemia of women in the OD-HA group and HA-PCOM group were significantly higher than those of women in the OD-PCOM group (p < 0.05). T concentration (>1.67 nmol/L) and Ferriman-Gallwey (F-G) score (>3) significantly increased the risk of metabolic disorders in women with PCOS (p < 0.05). The phenotypes of OD-HA and HA-PCOM in women with PCOS were vulnerable to metabolic disorders compared to OD-PCOM. Thus, the metabolic disorders in women with PCOS especially those with the HA phenotype should be paid more attention in order to reduce long-term complications.

Plasma FGF21 Concentration in Kidney Transplant Patients-Results from Prospective and Cross-Sectional Studies.

Background/Objectives: Fibroblast growth factor 21 (FGF21) is a protein hormone involved in physiological conditions in the regulation of energy expenditure and several metabolic processes. The aim of this present study was to analyze the effect of successful kidney transplantations on the plasma FGF21 concentration and to study the factors which may influence plasma FGF21 concentration in patients in long time after kidney transplantation. Methods: This study consisted of two independent parts. The first part was a prospective observation of CKD patients in stage 5 before and then on the 14th and 30th day and 6 months after kidney transplantation. The second part of this study was the cross-sectional study completed in patients at least one year after kidney transplantation and the control group. In CKD patients directly before and during the early period after KTx, plasma FGF21 concentrations were measured four times (immediately before and 14 and 30 days and 6 months after KTx). In patients long time after kidney transplantation and in healthy subjects, plasma FGF21 concentration was measured once. Results: Forty patients with chronic kidney disease (CKD) who were either directly before or within the early period after kidney transplantation (KTx), 184 patients longtime after KTx and 50 healthy subjects were enrolled into this study. In CKD patients at the stage directly before receiving a KTx, the mean plasma FGF21 concentration was significantly higher than in the healthy subjects [1013.0 pg/mL versus 239.5 pg/mL, p < 0.001]. At 14, 30 days, and 6 months after the KTx, a significant decrease of plasma FGF21 was observed, with values of 322.5 pg/mL; 355.0 pg/mL; and 344.0 pg/mL (p < 0.001), respectively]. In patients long time after KTx, a negative correlation was found between the plasma FGF21 concentration and the estimated glomerular filtration rate and a positive correlation was found between the plasma FGF21 concentration and the BMI, the serum concentration of triglycerides, insulin, interleukin-6, CRP, and cystatin C. Conclusions: The plasma FGF21 concentration in patients with end-stage renal disease is higher than in healthy subjects and significantly decreases after a successful KTx. The plasma FGF21 concentration measured by ELISA in patients long time after kidney transplantation seems to be related to the degree of kidney function impairment and their metabolic status. The kidneys appear to be one of the main organs involved in the biodegradation and/or elimination of FGF21.

Physiological Impacts of Energy Drink Consumption: A Clinical Analysis in Adolescents.

Energy drink (ED) consumption among Israeli-Arab adolescents is widespread. This study aimed to investigate the acute glycemic and insulin effects of EDs in healthy adolescents. Seventy-one Israeli-Arab adolescents (56% girls, average age 16.04 ± 1.03 years) participated in a non-randomized, case-controlled, open-label study. Participants consumed ED (n = 36) or a volume- and carbohydrate-matched non-caffeinated soft drink (SD, n = 35), followed by a 2 h glucose tolerance test. Blood glucose was measured at baseline and 15, 30, 60, and 120 min post-consumption (T0, T15, T30, T60 and T120, respectively). Serum insulin concentration and caffeine relative intensity were determined 45 min post-consumption (T45). Blood glucose levels peaked significantly at T15 and remained significantly higher at T30 in the ED group compared to the SD group (p = 0.005, p = 0.017, respectively). Insulin concentrations were substantially higher at T45 in the ED group (t [64] = 2.794, p = 0.001). This pattern was especially prominent in heavy ED consumers. A positive correlation emerged between the amount of caffeine consumed (mg/kg), blood glucose levels at T15 and T30, and insulin concentration at T45. This study is the first to demonstrate the glycemic and insulin responses to ED consumption in adolescents, suggesting that regulatory measures limiting ED sales to adolescents could improve their health.

Effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome: a randomized controlled trial

ObjectiveThe aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS).MethodsA total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters.ResultsThe serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). The BMI, WHR, insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower compared with control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was observed in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05).ConclusionVitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance.

The addition of mycoprotein to a mixed-meal impacts postprandial glucose kinetics without altering blood glucose concentrations: a randomised controlled trial

BackgroundMycoprotein is a high-fibre food previously shown to reduce postprandial glucose concentrations when ingested within a mixed-meal. We applied a dual stable isotope tracer approach to determine whether this is due to a reduced rate of appearance of glucose, in participants of ranging BMI.MethodsTwenty-four adults (F = 8, BMI 30 ± 6 kg·m−2) attended 2 trials in a double-blind, randomised, cross-over design. Participants ingested two energy and macronutrient matched milk-based drinks (enriched with 1000 mg [U-13C6] glucose in a subset of 12 participants), containing 50 g glucose and either 0 (CON) or 20 g (MYC) mycoprotein. A primed continuous intravenous infusion of D-[6,6-2H2] glucose determined plasma glucose kinetics over 6 h. Postprandial time-course, and AUC, of glucose and insulin concentration, rate of disappearance (RdT) and appearance of exogenous (RaEx), endogenous (EGP), and total (RaT) plasma glucose were assessed using two- and one-way ANOVA.ResultsDrink ingestion increased blood glucose and serum insulin concentrations (P < 0.05) and were comparable between conditions (P > 0.05). Both RaT and RdT were higher with MYC compared with CON over 6 h (mean 6 h glucose appearance and disappearance increased by 5 and 9%, respectively, P < 0.05). RaEx was not affected by MYC ingestion over 6 h (P > 0.05). The mean contribution of EGP to total glucose appearance was 15% greater with MYC, with a trend towards significance (P = 0.05). There was no relationship between BMI and the response to MYC ingestion for any of the variables (P < 0.05).ConclusionThe ingestion of mycoprotein within a mixed-meal impacted postprandial glucose kinetics, but not blood glucose or serum insulin concentrations, in individuals of ranging BMI.Clinical trial registry number and websiteThis trial was registered at clinicaltrials.gov as NCT04084639 and can be accessed at https://clinicaltrials.gov/ct2/show/NCT04084639.

Insulinoma presenting with anti-insulin antibodies.

An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies. Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

Effects of electrical stimulation of the lower extremities on postprandial hyperglycemia and arterial stiffness.

To compare the acute effects of electrical stimulation (ES) of the lower extremities on postprandial hyperglycemia and arterial stiffness during oral glucose tolerance testing (OGTT). In a randomized crossover study, eight healthy young men completed three experimental trials in which they underwent ES for 30 min, starting 60 min before (Before) or 30 min after (After) ingesting 75 g of glucose; ES was not performed in the control trial (Control). The subjects' blood glucose levels and brachial-ankle pulse wave velocity (baPWV) were measured as an index of arterial stiffness at baseline and 30, 60, and 120 min after glucose ingestion. Serum insulin levels were measured at baseline and 60 min after glucose ingestion. The subjects' glucose intake led to an increase in their blood glucose concentration in all trials, however, in the After trial, ES resulted in significantly lower blood glucose concentrations at 60 min post glucose ingestion compared to the Control and Before trials. The area under the curve (AUC) of serum insulin concentrations during the OGTT in the After trial was significantly lower than that in the other two trials. Moreover, glucose ingestion did not increase the baPWV, however, 30 min of ES during the postprandial state acutely reduced the baPWV. These results suggest that ES is most effective in reducing postprandial hyperglycemia when administered after a meal. Thus, lower extremity ES may be an alternative exercise method to activate postprandial glucose metabolism in healthy individuals.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.

Adipocyte-specific FAK deletion promotes pancreatic β-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.

White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown. We generated adipocyte-specific FAK KO (FAK-AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic β-cells were proposed in FAK-AKO mice and validated by cell line studies using 3T3-L1, Raw264.7 and Min6. The FAK-AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases β cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ-induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic β cell area. Moreover, serum pro-inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3-L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS-treated RAW264.7 macrophages with knockdown FAK of 3T3-L1 adipocytes increased macrophage pro-inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF-κB signaling, which exacerbates inflammation of adipocytes themselves. Adipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro-inflammatory factors released by the FAK-null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK-mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.

The effect of sucrose consumption on eating behavior and depression during morphine withdrawal period in rats

BACKGROUND: Sugary drink and junk food consumption increases during the withdrawal period, leading to subsequent psychological and metabolic alterations. OBJECTIVES: We aimed to investigate the relationship of sucrose consumption with serum insulin levels, leptin levels, brain Dopamine-2 receptor (D2R) expression, food consumption, and anxiety-depression findings in morphine-withdrawal rats. METHODS: Thirty-six male Wistar albino rats were divided into six groups: Control, sucrose-free, 5% sucrose, 10% sucrose, 20% sucrose, and an addiction test. Saline was intraperitoneally injected to the control group, and morphine was intraperitoneally injected to the other groups for 14 days. After 14 days, naloxone was administered to the addiction test group, and addiction symptoms were observed and this group was sacrificed on the same day. Other groups were fed ad libitum with different concentrations of sucrose solution for one week. Behavioral parameters were evaluated at the end of the experiment. Leptin and insulin concentrations in serum and D2R levels in brain tissues were detected using an enzyme-linked immunosorbent assay. D2R concentrations in brain tissues were evaluated utilizing immunohistochemistry. RESULTS: We observed decreased food consumption and increased fluid consumption in rats that consumed sucrose water during the withdrawal period. The level of depression and binge eating behavior was elevated in groups consuming sucrose, and the 10% sucrose group had the highest carbohydrate consumption and anxiety levels. In addition, the 10% sucrose group had the lowest brain D2R expression. The leptin level was highest in the 20% sucrose group. CONCLUSIONS: These results show the possible effects of sugary drinks consumed during the withdrawal period.

Fermented red pepper paste (kochujang) modulates glucose metabolism and gut microbiota in parasympathetic suppression: Network pharmacology and In vivo study

We aimed to explore the relationship between Korean fermented red pepper paste, kochujang compounds, and the genes associated with type 2 diabetes (T2DM) and parasympathetic nervous system (PNS) dysfunction by network pharmacology. The study aimed to validate the kochujang efficacy on glucose metabolism in PNS-suppressed rats. Male Sprague-Dawley rats were intraperitoneally injected with scopolamine at 2 mg/kg body weight daily for 8 weeks. They were divided into four groups according to kochujang types: 1% traditionally-made kochujang (TMK) in 43% fat diets based on the capsaicin content and factory-made kochujang (FMK). The control and normal-C groups received a 43% fat diet. In the network pharmacology analysis, kochujang contained 26 chemical compounds: carotenoids, isoflavonoids, capsaicin-related compounds, and phytosterols. It highlighted critical genes, including AKT1, B-cell lymphoma-2(BLC2), catenin beta-1(CTNNB1), and caspase-3(CASP3) as the primary targets for treating T2DM and PNS suppression. Functional enrichment analysis indicated the involvement of kochujang compounds in endopeptidase activity and G-protein-coupled receptor activity relevant to diabetes and neuropathy. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed associations with cancer, infection and inflammation, lipid metabolism, and diabetic complication-related pathways. FMK and TMK consumption improved glucose homeostasis and lipid profiles by modulating serum insulin and glucagon-like peptide-1 concentration and insulin resistance in scopolamine-induced rats. Oral glucose tolerance tests showed reduced glucose intolerance in kochujang-treated groups, especially high capsaicin-containing TMK. Kochujang mitigated liver damage and inflammation and modulated the gut microbiota composition to prevent the inhibition of insulin and neurotransmitter secretion through potentiating cAMP and calcium signaling pathways. In conclusion, high capsaicin-containing kochujang exhibited promising therapeutic effects against T2DM induced by PNS suppression through gut microbiota modulation.

Control of Weıght, Insulın Resıstance and Oxıdatıve Stress in Rats Fed Hıgh-Fat Dıet Usıng Aframomum melegueta (Allıgator Pepper)

Consumptions of diets rich in fat is very predominant due to the sensational values it adds to the foods. If overconsumed, such foods lead to metabolic diseases. Inclusion of alligator pepper in the diets as means of ameliorating such diseases was investigated. Thirty-six (36) Wistar rats were divided into 6 groups. Groups 1, 2, 3 and 4 received standard diet, high fat diet (HFD), 1% and 2% alligator pepper-supplemented standard diet respectively. Groups 5 and 6 got 1% and 2% alligator pepper-supplemented HFD respectively. The groups were fed ad libitum for 8 weeks. Blood glucose level, body weights, activities of antioxidant enzymes and serum concentrations of malondialdehyde (MDA) and insulin were determined. homeostasis model assessment of insulin resistance (HOMA-IR) was computed. The groups that received alligator pepper-supplemented HFD had significantly (p&lt;0.05) higher final average weight, insulin level and HOMA-IR in comparison with the control but lower ın these parameters when compared with the HFD-group. All the groups fed supplemented diets had significantly (p&lt;0.05) higher serum catalase activities in comparison with the HFD group. Also, all, except the group fed 1% alligator pepper-supplemented HFD had significantly (p&lt;0.05) higher superoxide dismutase activities than the HFD group. It is concluded that including the pepper in the standard diet may have no special advantages in respects of the studied parameters, but could decrease weight gain, improve insulin sensitivity and oxidative stress defense mechanism in rats fed HFD.

The Potency of Antidiabetic of Psidium guajava Fruit Extract Against Streptozotocin-induced Type 2 Diabetic Rats

Background: The chronic disease known as diabetes mellitus is brought on by either the pancreas's inability to make enough insulin or the body's inability to use it. Purpose: This plant finds applications for treating diarrhea, dysentery, gastroenteritis, hypertension, diabetes, caries and pain relief. Purpose: The current study aimed to determine how Psidium guajava fruit extract affected the blood glucose, body weights, and insulin levels of streptozotocin (STZ)-induced diabetic rats over 21 days. Methods: The extract's effectiveness was compared to that of glibenclamide, a common hypoglycemic medication. 30 male Wistar albino rats were divided into 5 groups with 6 animals in each group. V: Normal control (Group-I), diabetic control (Group-II), diabetic rats treated with glibenclamide 0.6mg/kg bw (Group-III), diabetic rats treated with Psidium guajava fruit extract 200 mg/kg bw (Group-IV) and Psidium guajava fruit extract 400 mg/kg bw (Group-V). All group of rats were subjected to evaluation of body weight, blood glucose and serum insulin levels on day 0, 7, 14 and 21 of the experiment. Results: There was significant (P&lt;0.05) decrease in body weight and serum insulin and significant (P&lt;0.05) increase in blood glucose level in Group-II compared to Group-I rats. In the Present study, daily oral administration of Psidium guajava fruit extract at dose rate of 200 and 400 mg/kg bw and glibenclamide at 0.6mg/kg bw in diabetic rats for 21 days showed a progressive improvement in body weight, blood glucose and serum insulin concentration. Conclusion: It can therefore be concluded the results of this study indicate that Psidium guajava fruit extract possesses anti-diabetic properties in Wistar albino rats.

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PurposeThe aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. MethodsA T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. ResultsTreatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). ConclusionMlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Impact of dietary protein and energy levels on fatty acid profile, gut microbiome and cecal metabolome in native growing chickens

The present study investigated the optimal concentration of dietary ME and CP for the fatty acid profile of meat, gut microbiome, and cecal metabolome in Danzhou chickens from 120 to 150 d of age. A total of seven hundred and twenty 120-d-old Danzhou female chickens, with a similar BW, were randomly allocated into 6 treatments with 6 replicates and each of 20 birds. The chickens were fed 2 levels of dietary ME (11.70 MJ/kg, 12.50 MJ/kg), and 3 levels of dietary CP (13%, 14%, and 15%). The results showed that dietary ME and CP levels didn't affect final BW, ADG, ADFI, and feed gain ratio (g: g) (P > 0.05). The serum concentrations of triglyceride, insulin, and glucose in the 12.50 MJ/kg group were the highest (P < 0.05). Dietary ME, CP levels, and their interactions affected (P < 0.05) the fatty acid content in the breast muscle, thigh muscle, and liver. The levels of C18:0, C20:0, C22:0, C22:1, C18:2, C18:3, C22:6, and SFA of the liver in the high ME group were higher than those in the low ME group (P < 0.05). The levels of C16:0, C14:1, C18:1, C22:5, SFA, MUFA and USFA in the low CP group were higher than the corresponding values in the other groups (P < 0.05). Dietary ME and CP levels altered the composition and relative abundance of microbiota in the cecum of chickens at various taxonomic levels to different extents. Significant effects of interactions were found between dietary ME and CP on the relative abundance of 10 species (P < 0.05), and among these species, 6 species belonged to the genus Bacteroides. Notably, the relative abundance of 2 probiotic species including Lactobacillus crispatus and Lactobacillus salivarius was significantly increased (P < 0.05) with increasing dietary ME level. There were 6 differential metabolites in the cecum, comprising thromboxane A2, 5,6-DHET, prostaglandin D2, 20-hydroxyeicosatetraenoic acid, 12(S)-HPETE and prostaglandin I2 significantly reduced (P < 0.05) with increasing the dietary ME level; all of them are involved in arachidonic acid metabolism. In conclusion, the present study suggested that the dietary levels of 12.50 MJ/kg ME and 14% CP enhanced meat quality in terms of fatty acid composition, and showed benefits for maintaining intestinal health via positive regulation of cecal microbiota in native growing Danzhou chickens.