Insulin Sensitivity Research Articles

LCoRL Regulates Growth and Metabolism.

Genome-wide association studies (GWAS) in humans and livestock have identified genes associated with metabolic traits. However, the causality of many of these genes on metabolic homeostasis is largely unclear due to a lack of detailed functional analyses. Here we report ligand-dependent corepressor-like (LCoRL) as a metabolic regulator for body weight and glucose homeostasis. Although GWAS data show that LCoRL is strongly associated with body size, glucose homeostasis, and other metabolic traits in humans and livestock, functional investigations had not been performed. We generated Lcorl knockout mice (Lcorl-/-) and characterized the metabolic traits. We found that Lcorl-/- pups are born smaller than the wild-type (WT) littermates before reaching normal weight by 7 to 9 weeks of age. While aging, Lcorl-/- mice remain lean compared to WT mice, which is associated with a decrease in daily food intake. Glucose tolerance and insulin sensitivity are improved in Lcorl-/- mice. Mechanistically, this stunted growth is linked to a reduction of circulating levels of IGF-1. The expression of the genes downstream of GH signaling and the genes involved in glucose and lipid metabolism are altered in the liver of Lcorl-/- mice. Furthermore, Lcorl-/- mice are protected against a high-fat diet challenge and show reduced exercise capacity in an exercise stress test. Collectively, our results are congruent with many of the metabolic parameters linked to the Lcorl locus as reported in GWAS in humans and livestock.

VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome.MethodsIn this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway.ResultsWe observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis.ConclusionsOur studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor.Graphical

The Potential Role of Beetroot Juice in Hyperglycemia Management: A Review of Mechanisms and Clinical Outcomes

Hyperglycemia, characterized by elevated blood glucose levels, is a significant health concern that affects millions of individuals worldwide. It has been associated with long-term complications affecting the cardiovascular, renal, and nervous systems. Beetroot juice (BRJ), rich in nitrates, betalains, and antioxidants, has gained attention for its potential role in mitigating hyperglycemia and improving insulin sensitivity. This review evaluates the available scientific evidence on the hypoglycemic effects of beetroot juice, explores its proposed mechanisms of action, and discusses its potential as a complementary therapy for diabetes management. By analyzing studies, we found that beetroot juice may help manage hyperglycemia by enhancing insulin sensitivity through its nitrate content, which converts to nitric oxide. Clinical evidence indicates it may lower fasting blood glucose and improve glycated hemoglobin A1c (HbA1c) levels, though results vary. While beetroot juice shows promise as a supplementary treatment for hyperglycemia, more research is needed to determine the optimal dosage, long-term effects, and interactions with other diabetes management strategies.

Anti-Diabetic Effects of Oleuropein

Background/Objectives: Oleuropein, a secoiridoid polyphenol found in olive oil as well as the fruit and leaves of the olive tree, has been reported to have antioxidant, cardioprotective, anti-inflammatory, anti-cancer, and anti-diabetic properties. Type 2 diabetes mellitus (TD2M) is a chronic metabolic disease characterized by impaired insulin action, termed insulin resistance. The development of T2DM is closely associated with obesity and chronic low-grade inflammation. In recent years, a rise in sedentary lifestyles and diets rich in refined carbohydrates and saturated fats has contributed to an increase in the prevalence of obesity and TD2M. Currently, the strategies for treating T2DM and its prevention lack efficacy and are associated with adverse side effects. Hence, there is an urgent need for novel treatment strategies, including naturally occurring compounds possessing hypoglycemic and insulin-sensitizing properties. Methods: This review summarizes the evidence of the anti-inflammatory and anti-diabetic properties of oleuropein from in vitro and in vivo animal studies, as well as the available clinical trials. Results: The existing evidence indicates that oleuropein may exert its anti-inflammatory effects by downregulating the levels of pro-inflammatory cytokines in hepatic and adipose tissue. Additionally, the evidence suggests that oleuropein targets skeletal muscle and enhances glucose uptake and its related protein signalling cascades, improving glucose tolerance and insulin sensitivity. Conclusions: Despite the evidence of oleuropein’s anti-inflammatory and anti-diabetic potential, more animal and clinical studies are needed to proceed towards its clinical/therapeutic use for metabolic diseases confidently.

Correlation between portal hypertension and somatic constitution: rationale behind the concept

This review summarizes recent data on the correlation of somatic constitution and portal hypertension.Somatotype reflects the constitutional composition of the human body. Excess endomorphic component (i.e. obesity) increases the risk of portal hypertension (PH - elevated pressure in the portal system above 12 mmHg) development. Among the prehepatic and posthepatic PH causes only congestive hepatopathy, a consequence of heart failure, is connected with obesity. A number of pathways connect the hepatic PH causes with obesity. Firstly, the action of proinflammatory cytokines produced by adipose tissue in greater amount in obesity promotes fatty acid uptake and storage by hepatocytes, leading to elevated oxidative stress and metabolic dysfunctions, activation of stellate cells, that differentiate into myofibroblasts and produce components of the intercellular matrix such as collagen into the perisinusoidal space resulting in fibrosis. Secondly, insulin resistance associated with obesity promotes dysfunction of the hepatic microcirculatory blood vessels, hyperlipidemia and liver steatosis. Thirdly, AMISS (Absence of Meal-induced Insulin Sensitization Syndrome), caused by regular high-carbohydrate and low-protein food consumption, manifested in decreased postprandial secretion of hepatic hormone hepatalin, which increases glucose uptake by skeletal and cardiac muscle, results in prolonged postprandial hyperglycemia, compensatory hyperinsulinemia and hyperlipidemia, leading to increased insulin resistance and a prediabetic state, associated with steatohepatosis. Thus, excess endomorphic component is to be regarded as a prognostic factor for portal hypertension.

Metformin in gestational diabetes: physiological actions and clinical applications.

Metformin is an effective oral hypoglycaemic agent used in the treatment of type 2 diabetes mellitus; however, its use in pregnancy for the treatment of gestational diabetes mellitus (GDM) remains controversial owing to concerns around safety and efficacy. This comprehensive review outlines the physiological metabolic functions of metformin and synthesizes existing literature and key knowledge gaps pertaining to the use of metformin in pregnancy across various end points in women with GDM. On the basis of current evidence, metformin reduces gestational weight gain, neonatal hypoglycaemia and macrosomia and increases insulin sensitivity. However, considerable heterogeneity between existing studies and the grouping of aggregate and often inharmonious data within meta-analyses has led to disparate findings regarding the efficacy of metformin in treating hyperglycaemia in GDM. Innovative analytical approaches with stratification by individual-level characteristics (for example, obesity, ethnicity, GDM severity and so on) and treatment regimens (diagnostic criteria, treatment timing and follow-up duration) are needed to establish efficacy across a range of end points and to identify which, if any, subgroups might benefit from metformin treatment during pregnancy.

Relationship of Plasma Apolipoprotein C-I Truncation With Risk of Diabetes in the Multi-Ethnic Study of Atherosclerosis and the Actos Now for the Prevention of Diabetes Study.

Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I'/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown. Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] ≥7.0 mmol/L or hypoglycemic medication use in MESA; FG ≥7.0 mmol/L or 2-h glucose ≥11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) and Matsuda insulin sensitivity index (ISI) in ACT NOW. In MESA, a higher C-I'/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (-0.5%; P < 0.0001) and HOMA-IR (-2.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I'/C-I was associated with smaller increases in AUCglucose (-1.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids. Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes.

GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice.

Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/-) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

Time-restricted feeding mediated modulation of microbiota leads to changes in muscle physiology in Drosophila obesity models.

Recent research has highlighted the essential role of the microbiome in maintaining skeletal muscle physiology. The microbiota influences muscle health by regulating lipid metabolism, protein synthesis, and insulin sensitivity. However, metabolic disturbances such as obesity can lead to dysbiosis, impairing muscle function. Time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, but its effects on restoring healthy microbiomes remain poorly understood. This study utilizes 16S microbiome analysis and bacterial supplementation to investigate the bacterial communities influenced by TRF that may benefit skeletal muscle physiology. In wild-type and obese Drosophila models (axenic models devoid of natural microbial communities), the absence of microbiota influence muscle performance and metabolism differently. Specifically, axenic wild-type Drosophila exhibited reduced muscle performance, higher glucose levels, insulin resistance, ectopic lipid accumulation, and decreased ATP levels. Interestingly, in obese Drosophila (induced by a high-fat diet or predisposed obesity mutant Sk2), the absence of microbiota improved muscle performance, lowered glucose levels, reduced insulin resistance, and increased ATP levels. TRF was found to modulate microbiota composition, notably increasing Acetobacter pasteurianus (AP) and decreasing Staphylococcus aureus (SA) in both obesity models. Supplementation with AP improved muscle performance and reduced glucose and insulin resistance, while SA supplementation had the opposite effect. This study provides novel insights into the complex interactions between TRF, microbiota, and skeletal muscle physiology in different Drosophila models.

Heterogeneity of gestational diabetes and risk for adverse pregnancy outcome: a cohort study.

Diabetes has increasingly been recognized as a heterogeneous disease, with clinical characteristics and outcomes risk varying across different phenotypes. Evidence on heterogeneity of gestational diabetes (GDM) is yet to be provided. To investigate the insulin physiology and pregnancy outcomes of GDM phenotypes characterized by fasting hyperglycemia or postload hyperglycemia. A total of 2050 women who underwent a 75-g oral glucose tolerance test were prospectively recruited and followed up until delivery. Women were categorized into normoglycemia (NGT, n = 936), isolated impaired fasting glucose (gestational-IFG, n = 378), and isolated impaired postload glucose tolerance (gestational-IGT, n = 736) groups. Fasting blood sample at mid-pregnancy were collected to measure C-peptide and insulin concentrations. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate insulin physiology. Maternal and neonatal outcomes were recorded. Gestational-IFG had greater insulin resistance (HOMA-IR 3.11 vs. 2.25, QUICKI-CP 0.94 vs. 1.03, both P < 0.01), and gestational-IGT had worse β-cell function (C-peptide 2.00 vs. 2.26 ng/ml, P < 0.05) when compared to one another. Gestational-IFG was more strongly associated with excessive gestational weight gain (RR 1.62, 95% CI 1.18-2.23) and large-for-gestational-age infants (RR 1.45, 95% CI 1.03-2.03) than gestational-IGT. The risk for neonatal brain injury was increased in gestational-IGT (RR 2.03, 95% CI 1.04-4.09), but not in gestational-IFG (P = 0.439). Gestational-IGT showed a stronger association with the risk of preterm birth compared to gestational-IFG (RR 1.80, 95% CI 1.02-3.36). GDM exhibits distinct insulin physiology profiles. Pregnancy outcome varies between each phenotype. These findings provide evidence on risk stratification and diverse strategies for the treatment of GDM.

Prolonged treatment of compactin, atorvastatin, lovastatin or simvastatin decreased glucose consumption and expressions of proteins for glucose metabolism and insulin signaling in L6 skeletal muscle cells

Statins inhibit mevalonate synthesis and successfully lower plasma cholesterol levels and decrease the risk of cardiovascular diseases in humans, but also lead to myalgia in some patients. We hypothesize that statins may modulate glucose metabolism and insulin signaling in the skeletal muscle cells during and after differentiation, and in turn lead to side effects. Here, differentiating and differentiated L6 muscle cells were treated with 1 μM of different class of statins (compactin, pravastatin, atorvastatin, lovastatin and simvastatin) with or without insulin or mevalonate for extended periods of time. The glucose consumption and expression levels of proteins for glucose metabolism and insulin receptor (IR)/Akt signaling were determined. The prolonged statin treatments (except pravastatin) decreased glucose consumption in L6 skeletal muscle cells. In differentiating L6 cells, compactin, lovastatin or simvastatin decreased the expression levels of proteins involved in glucose metabolism and insulin signaling, including glucose transporter 4 (GLUT4), pyruvate dehydrogenase (PDH), glycogen synthase (GS), glycogen synthase kinase 3β (GSK3β) and insulin receptor β subunit (IRβ). In differentiated L6 cells, long-term treatment of compactin or simvastatin also decreased levels of proteins in glucose metabolism and IR/Akt signaling, including GLUT4, GSK3β, IRβ and PI3K p110α. Insulin treatment restored statin-mediated impairments in L6 cells. The insulin-mediated phosphorylation of Akt Ser473 was attenuated in differentiating and differentiated L6 cells in the presence of atorvastatin (differentiated only), compactin, lovastatin or simvastatin. In addition, mevalonate supplementation reversed the statin-mediated impairments in differentiated and differentiating L6 cells. Statin affected glucose usage and insulin signaling by inhibiting mevalonate synthesis in L6 cells. Our results provides a possible mechanism of adverse effects of statins in skeletal muscle and calls for cautious use of the medication in patients with impaired insulin sensitivity and glucose metabolism.

Effect of antenatal use of high energy nutritional supplements on cardio metabolic risk markers in underweight primi gravidas; a randomized controlled trial

BackgroudPregnancy is a state of increased metabolic demand, and poor maternal nutrition can exacerbate these changes, potentially increasing the risk of cardiometabolic disorders.This study is significant as it investigates the effect of high energy nutritional supplements on cardio metabolic risk markers in underweight primigravidas.MethodologyA single blinded randomized controlled trial was conducted from April 2018- August 2019 among the Pakistani tertiary care facilities of Khyber Pakhtunkhwa. A total of thirty six participants were randomized into two groups receiving either high energy nutritional supplement ‘MAAMTA’ or Placebo. They were instructed to take Placebo/Supplement alongside to their regular prenatal care and food from their first antenatal visit till a week postnatally. Anthropometric measurements and blood samples for biochemical parameters insulinlevels, fasting blood glucose & lipid profile were taken at baseline visit, between 16 and 20 weeks gestation and a post natal visit.ResultsThe two-way repeated measures ANOVA showed that there was a highly significant time effect on participant’s Insulin level (F (1.8, 53.6) = 10.64, P < 0 0.000, ηp2 = 0.269). A highly significant time effect on participant’s insulin resistance (F (2, 68) = 8.116,P < 0 0.001, ηp2 = 0.193) was also observed. There was a highly significant time effect on participant’s LDL level as well (F (2, 68) = 11.82, P < 0 0.000, ηp2 = 0.258).ConclusionSupplementation with high energy nutritional supplements may improve insulin levels and insulin sensitivity in underweight primigravidas.Trial registrationhttps://www.ClinicalTrials.govClinicalTrials.gov Identifier: ISRCTN 10088578. Registered on 27 March 2018. https://www.isrctn.com/ISRCTN10088578.

Impact of lifestyle intervention on vitamin D, Adiponectin, Insulin-like growth factor 1 and Proneurotensin in overweight individuals from the Middle East

BackgroundImmigrants from the Middle East (ME) have a higher prevalence of type 2 diabetes (T2D) compared to the native-born Swedish population. In individuals free from T2D, ME immigrants are more insulin resistant and have lower levels of adjusted insulin secretion (Disposition index, DIo) compared to Swedish-born individuals. The ethnic differences are not fully explained by traditional risk factors. This has raised the question as to whether hormonal factors other than insulin are involved, contributing to higher T2D risk in ME immigrants. AimsIn ME immigrants at high risk of developing T2D, we aimed to study the effect of a randomized culturally adapted lifestyle intervention on the levels of Vitamin D (25(OH)D), insulin-like growth factor 1 (IGF-1), Pro-neurotensin (Pro-NT) and Adiponectin. Furthermore, we aimed to study if the effect of the intervention was associated to these hormones, or if a direct effect of the intervention remained after accounting for these. MethodsIn this culturally adapted randomized controlled trial of four months duration, eligible ME immigrants at high risk of developing T2D identified in the MEDIM cohort were invited to participate. The intervention group (N= 35) received a culturally adapted lifestyle intervention program consisting of seven group sessions and cooking classes. The control group (N= 32) were given treatment as usual with oral and written information to improve their lifestyle habits. Using mixed models’ linear regression analysis, the changes in the levels of 25(OH)D, IGF-1, Adiponectin and Pro-NT were assessed by comparing the groups and we further studied the effects of the changes on insulin action and secretion. ResultsThe adjusted levels of 25(OH)D significantly increased in the intervention group compared to the control group (β for the effect of the intervention on 25(OH)D: 0.061, 95% CI 0.009-0.113, P = 0.023). The increase in insulin sensitivity index (ISI) observed in the intervention compared to the control group was altered after adjusting for 25(OH)D: 0.129, 95% CI -0.016-0.274, P = 0.078). IGF-1, Adiponectin and Pro-NT did not significantly influence the change over time concerning insulin secretion. ConclusionLifestyle intervention increases the adjusted levels of 25(OH)D. Moreover, the effect of the lifestyle intervention on insulin action and secretion was altered when adjusting for 25(OH)D.

The Application and Research of Probiotics in the Treatment of Diabetes

This review explores the application and research progress of probiotics in the treatment of diabetes. With the rising incidence of diabetes, traditional treatments face numerous challenges, including side effects of medications and poor patient compliance. As a novel therapeutic approach, probiotics have shown potential in improving glycemic control, enhancing insulin sensitivity, and lowering inflammation levels. Research indicates that probiotics can regulate the gut microbiome, improve intestinal barrier function, promote nutrient absorption, and thus affect overall metabolic status. Furthermore, the antioxidant properties of probiotics have shown positive effects in protecting pancreatic cells and alleviating diabetes complications. Recent clinical trials have further supported the application of probiotics in diabetes management, especially in improving renal function, neuropathy, and cardiovascular health. Despite the optimistic results of existing studies, more high-quality randomized controlled trials are needed to establish the specific effects and optimal use strategies of different probiotics. This review provides a theoretical basis for future research and emphasizes the importance and potential of probiotics in the treatment of diabetes.

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

In type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism. Young adults with T1D (n = 30) and healthy controls (HC, n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA sequencing, and spatial metabolomics to assess this relationship. Participants with T1D had significantly higher glomerular basement membrane thickness compared to HC. T1D participants exhibited lower insulin sensitivity and cortical oxidative metabolism, correlating with higher insulin sensitivity. Proximal tubular transcripts of TCA cycle and oxidative phosphorylation enzymes were lower in T1D. Spatial metabolomics showed reductions in tubular TCA cycle intermediates, indicating mitochondrial dysfunction. The Slingshot algorithm identified a lineage of proximal tubular cells progressing from stable to adaptive/maladaptive subtypes, using pseudotime trajectory analysis, which computationally orders cells along a continuum of states. This analysis revealed distinct distribution patterns between T1D and HC, with attenuated oxidative metabolism in T1D attributed to a greater proportion of adaptive/maladaptive subtypes with low expression of TCA cycle and oxidative phosphorylation transcripts. Pseudotime progression associated with higher HbA1c, BMI, GBM, and lower insulin sensitivity and cortical oxidative metabolism. These early structural and metabolic changes in T1D kidneys may precede clinical DKD. gov NCT04074668.

Repetitive transcranial magnetic stimulation elicits weight loss and improved insulin sensitivity in type 2 diabetic rats.

Type 2 diabetes (T2D) accounts for the majority of diabetes incidences and remains a widespread global chronic disorder. Apart from early lifestyle changes, intervention options for T2D are mainly pharmaceutical. Repetitive transcranial magnetic stimulation (rTMS) has been approved by the FDA as a therapeutic intervention option for major depressive disorders, with further studies also indicating its role in energy metabolism and appetite. Considering its safe and non-invasive properties, we evaluated the effects of rTMS on systemic metabolism using T2D rats. We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure. Improved systemic insulin sensitivity was maintained after a 21-day treatment period, accompanied by modest yet significant weight loss. Circulating serum lipid levels, including those of cholesteryl ester, tryglyceride and ceramides, were also reduced following rTMS application. RNA-seq analyses further revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism. Altered expression of hypothalamic genes that are related to appetite regulation, neural activity and ether lipid metabolism were also implicated. In summary, our data report a positive impact of rTMS on systemic insulin sensitivity and weight management of T2D rats. The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.

Health Benefits Beyond the Scale: The Role of Diet and Nutrition During Weight Loss Programmes.

Obesity management strategies such as caloric restriction, very-low-calorie diets (VLCDs), and meal replacements can lead to moderate short-term weight loss. However, many patients face significant challenges in maintaining these results. Personalized interventions, including behavioral counseling and physical activity, have been shown to improve long-term adherence and success. Current clinical guidelines emphasize the pivotal role of dietitians in enhancing patient outcomes through nutritional therapy. When combined with pharmacotherapy and bariatric surgery, the focus shifts from mere weight loss to broader health improvements. This review explores the evolving role of dietitians in obesity management, advocating for a shift from a weight-centric approach to a more holistic model that prioritizes overall health gains. Key areas of interest include dietetic interventions' impact on metabolic health, cardiovascular function, gut microbiome balance, inflammation, and psychological well-being. Dietetic interventions have been shown to provide significant health improvements beyond weight loss. These include enhanced metabolic and cardiovascular health, better gut microbiome balance, reduced inflammation, improved sleep quality, mental well-being, and overall quality of life. By focusing on non-scale victories such as improved insulin sensitivity, lipid profiles, and mental health, dietitians play a crucial role in driving long-term success in obesity management. These outcomes highlight the need to shift the focus from short-term weight loss to a more comprehensive view of health gains. The role of dietitians in obesity management is expanding to encompass a more comprehensive and individualized approach. Moving beyond a focus on weight reduction, this paradigm promotes long-term, patient-centered strategies that address the multifactorial nature of obesity. By combining dietary changes with regular physical activity and behavioral support, dietitians can contribute to sustained health improvements, treating obesity as a chronic, complex disease.

Repurposing expired metformin to fluorescent carbon quantum dots for ratiometric and color tonality visual detection of tetracycline with greenness evaluation

Repurposing expired drugs is highly significant as it prevents the accumulation of pharmaceutical wastes, optimizes resource usage, and reduces environmental harm. Metformin, used for type II diabetes, lowers blood sugar via decreasing liver glucose production and increasing muscle insulin sensitivity. However, the growing number of expired tablets annually necessitates a strategic approach for repurposing or reusing these tablets. Herein, we develop a simple hydrothermal approach for converting expired metformin to valuable fluorescent carbon quantum dots (m-CQDs) with sizes smaller than 10 nm. The m-CQDs displayed a blue emission at 420 nm when excited at 350 nm. Interestingly, when tetracycline (TC) was added, the blue emission diminished, and a greenish-yellow emission emerged at 530 nm. This emission tunning was the resulting of combination of inner filter effect and aggregation induced emission. Leveraging this dynamic emission tunning, we developed both ratiometric-based fluorescence and color tonality-based visual detection methods for detecting TC in pharmaceuticals and wastewater. More importantly, three assessment tools, ComplexMoGAPI, AGREE, and BAGI were used to evaluate the environmental sustainability of the proposed analytical method. The evaluation confirmed the sustainability of the method and the alignment with the greenness guidelines for analytical methods.

Comparison of protective effects of teneligliptin and luseogliflozin on pancreatic β-cell function: randomized, parallel-group, multicenter, open-label study (SECRETE-I study).

The aim of this study is to directly compare the effects of SGLT2 inhibitors and DPP-4 inhibitors on β-cell function in patients with type 2 diabetes. We conducted a 26-week, randomized, open-label, parallel-group study, including a 1-2 week drug washout period, in patients with type 2 diabetes with HbA1c ≥7.0% and <9.0% and BMI ≥20 kg/m2 despite treatment with a drug naïve or other than DPP-4 inhibitors or SGLT2 inhibitors. A total of 103 subjects were randomly assigned to receive once daily oral luseogliflozin (L) or teneligliptin (T). The primary endpoint was the effect of L vs. T on the change in logarithmus naturalis (Ln) disposition index (DI) (DI 0-120min; combining measures of insulin secretion and sensitivity) from baseline to week 25-26 (post intervention), which was calculated by conducting an oral glucose tolerance test. Ln DI 0-120min were improved in both groups: -0.46 ± 0.68 to -0.20 ± 0.59 (p=0.03) in L group and -0.26 ± 0.60 to -0.05 ± 0.62 (p=0.01) in T group. The change in Ln serum proinsulin/C-peptide ratio, a marker of β-cell dysfunction, was reduced in L group (1.63 ± 0.63 to 1.56 ± 0.68, p=0.16), but rather increased in T group (1.70 ± 0.75 to 1.90 ± 0.51, p=0.01), with significant difference between the two groups (-0.27; p=0.004). Improvement of disposition index in subjects with obese type 2 diabetes was comparable between luseogliflozin and teneligliptin. On the other hand, it is likely that alleviation of β-cell dysfunction is more effective with luseogliflozin compared to tenegliptin. https://rctportal.niph.go.jp/en, identifier jRCTs061190008.

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.