Insulin Action Research Articles

SGLT2 inhibitors: how do they affect the cardiac cells.

The first sodium-glucose cotransporter-2 inhibitor (SGLT2I), canagliflozin, was approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in 2013. Since then, other members of this drug class (such as dapagliflozin, empagliflozin, and ertugliflozin) have become widely used. Unlike classical antidiabetic agents, these drugs do not interfere with insulin secretion or action, but instead promote renal glucose excretion. Since their approval, many preclinical and clinical studies have been conducted to investigate the diverse effects of SGLT2Is. While originally introduced as antidiabetic agents, the SGLT2Is are now recognized as pillars in the treatment of heart failure and chronic kidney disease, in patients with or without diabetes. The beneficial cardiac effects of this class have been attributed to several mechanisms. Among these, SGLT2Is inhibit fibrosis, hypertrophy, apoptosis, inflammation, and oxidative stress. They regulate mitochondrial function and ion transport, and stimulate autophagy through several underlying mechanisms. This review details the potential effects of SGLT2Is on cardiac cells.

Physiological and metabolic functions of the β3-adrenergic receptor and an approach to therapeutic achievements.

A specific type of beta-adrenergic receptor was discovered in the decade of 1980s and subsequently recognized as a new type of beta-adrenergic receptor, called beta3-adrenoceptor (β3-AR). β3-AR expresses in different tissues, including adipose tissue, gall bladder, stomach, small intestine, cardiac myocytes, urinary bladder, and brain. Structurally, β3-AR is very similar to β1- and β2-AR and belongs to a G-protein coupled receptor that uses cAMP as an intracellular second messenger. Alternatively, it also activates the NO-cGMP cascade. Stimulation of the β3-AR increases lipolysis, fatty acid oxidation, energy expenditure, and insulin action, leading to anti-obesity and anti-diabetic activity. Moreover, β3-AR differentially regulates the myocardial contraction and relaxes the urinary bladder to balance the cardiac activity and delay the micturition reflex, respectively. In recent years, this receptor has served as an attractive target for the treatment of obesity, type 2 diabetes, congestive heart failure, and overactive bladder syndrome. Several β3-AR agonists are in the emerging stage that can exert novel pharmacological benefits in different therapeutic areas. The present review focuses on the structure, signaling, physiological, and metabolic activities of β3-AR. Additionally, therapeutic approaches of β3-AR have also been considered.

Refining Insulin on Board with netIOB for Automated Insulin Delivery.

Automated insulin delivery (AID) systems enhance glucose management by lowering mean glucose level, reducing hyperglycemia, and minimizing hypoglycemia. One feature of most AID systems is that they allow the user to view "insulin on board" (IOB) to help confirm a recent bolus and limit insulin stacking. This metric, along with viewing glucose concentrations from a continuous glucose monitoring system, helps the user understand bolus insulin action and the future "threat" of hypoglycemia. However, the current presentation of IOB in AID systems can be misleading, as it does not reflect true insulin action or automatic, dynamic insulin adjustments. This commentary examines the evolution of IOB from a bolus-specific metric to its contemporary use in AID systems, highlighting its limitations in capturing real-time insulin modulation during varying physiological states.

Methylglyoxal induces death in human brain neuronal cells (SH-SY5Y), prevented by metformin and dapagliflozin

Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer's disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50–75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.

Rutin alleviates advanced glycosylation end products-induced insulin resistance by inhibiting SOCS3/IRS1 and activating PI3K/AKT signaling pathways in HepG2 cells

The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells.

Ozenoxacin suppresses sebum production by inhibiting mTORC1 activation in differentiated hamster sebocytes.

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.

Erythrina subumbrans (Hassk) Merr. (Fabaceae) Inhibits Insulin Resistance in the Adipose Tissue of High Fructose-Induced Wistar Rats.

The twigs and roots of Erythrina subumbrans (Hassk). Merr. Was reported to possess antidiabetic activity by reducing the activity of α-glucosidase and α-amylase. TNF-α is a pro-inflammatory cytokine in obesity and diabetes mellitus (DM). It inhibits the action of insulin, causing insulin resistance. Adiponectin is an anti-inflammatory peptide synthesized in white adipose tissue (WAT) and its high levels are linked with a decreased risk of DM. However, information about the effect of Erythrina subumbrans (Hassk). Merr. on insulin resistance are still lacking. To obtain the effects of the ethanol extract of E. subumbrans (Hassk) Merr. leaves (EES) in improving insulin resistance conditions. The leaves were collected at Ciamis, West Java, Indonesia, and were extracted using ethanol 96%. The effects of EES were studied in fructose-induced adult male Wistar rats by performing the insulin tolerance test (ITT) and assessing blood glucose, TNF-α, adiponectin, and FFA levels. The number of WAT and BAT of the adipose tissues was also studied. The total phenols and flavonoids in EES were determined by the spectrophotometric method and the presence of quercetin in EES was analyzed using the LC-MS method. EES significantly reduced % weight gain, TNF-α levels, and increased adiponectin levels in fructose-induced Wistar rats. EES significantly reduced the FFA levels of fructose-induced Wistar rats and significantly affected the formation of BAT similar to that of metformin. All rats in EES and metformin groups improved insulin resistance as proven by higher ITT values (3.01 ± 0.91 for EES 100 mg/kg BW; 3.01 ± 1.22 for EES 200 mg/kg BW; 5.86 ± 3.13 for EES 400 mg/kg BW; and 6.44 ± 2.58 for metformin) compared with the fructose-induced group without treatment (ITT = 2.62 ± 1.38). EES contains polyphenol compounds (2.7638 ± 0.0430 mg GAE/g extract), flavonoids (1.9626 ± 0.0152 mg QE/g extract), and quercetin 0.246 µg/mL at m/z 301.4744. Erythrina subumbrans (Hassk). Merr. extract may have the potential to be further explored for its activity in improving insulin resistance conditions. However, further studies are needed to confirm its role in alleviating metabolic disorders.

Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3β. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

Hydrogel-based Drug Delivery System in Diabetes Management.

It is estimated that there are over 200 million people living with diabetes mellitus (DM) all over the world. It is a metabolic condition caused by decreased insulin action or secretion. Diabetes Mellitus is also known as Type 2 Diabetes Mellitus. Type 1 diabetes mellitus and type 2 diabetes mellitus are the two most common types of DM. Treatment for type 1 diabetes often consists of insulin replacement therapy, while treatment for type 2 diabetes typically consists of oral hypoglycemics. Conventional dosing schedules for the vast majority of these medications come with a number of drawbacks, the most common of which are frequent dosing, a short half-life, and low bioavailability. Thus, innovative and regulated oral hypoglycemic medication delivery methods have been developed to reduce the limitations of standard dose forms. The studies and reviews published under the title were looked up in several databases (including PubMed, Elsevier, and Google Scholar). Hydrogels made from biopolymers are three-dimensional polymeric networks that can be physically or chemically crosslinked. These networks are based on natural polymers and have an inherent hydrophilic quality because of the functional groups they contain. They have a very high affinity for biological fluids in addition to a high water content, softness, flexibility, permeability, and biocompatibility. The fact that these features are similar to those of a wide variety of soft living tissues paves the way for several potentials in the field of biomedicine. In this sense, hydrogels offer excellent platforms for the transport of medications and the controlled release of those drugs. Additionally, biopolymer-based hydrogels can be put as coatings on medical implants in order to improve the biocompatibility of the implants and to prevent medical diseases. The current review focuses on the most recent advancements made in the field of using biopolymeric hydrogels that are physically and chemically crosslinked, in addition to hydrogel coatings, for the purpose of providing sustained drug release of oral hypoglycemics and avoiding problems that are associated with the traditional dosage forms of oral hypoglycemics.

Study changes in insulin secretion depending on anthropometric, anamnestic and laboratory parameters using a univariate linear model

Insulin is a peptide hormone which is produced by β-cells of the pancreas. It is difficult to underestimate the effect of insulin, it has a significant impact on organs and systems. Insulin is a carbohydrate “conductor”, disorders of the regulation process of which lead to metabolic disorders and irreversible changes in the human body.Insulin resistance (IR) is a state of reduced response of tissues to the action of insulin, which leads to disorders, including the reproductive function of a woman. Long-term IR leads to the development of hyperandrogenism, as a result of which anovulatory cycles, hirsutism, skin problems, vaginal dysbiosis, and an increased rate of anxiety and depression.The objective: to determine the influence of anthropometric, anamnestic and laboratory indicators on insulin secretion before and after a load of 75 g of glucose.Materials and methods. The study included 82 women of early reproductive age. 52 women are involved in the main group, 30 women – in the control group. The patients signed an informed voluntary consent, and the main aspects of the study were explained to them. In the course of the research we developed a questionnaire and conducted a survey.Anthropometric parameters (height, body weight, waist circumference) were measured, and BMI was calculated. Laboratory indicators were studied: luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), thyroid-stimulating hormone (TSH), prolactin, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone, free testosterone index, HOMA-IR index, glucose tolerance test (GTT) + determination of insulin level, Matsuda index.Results. The conducted correlation analysis proved the relationship between the level of fasting insulin and the following indicators: WC – r = 0.321900051, BMI – r = 0.333470666, establishment of the menstrual cycle – r = -0.283517408, duration of bleeding during menstruation, TSH level – r = 0.249578215, DHEA-S – r = -0.209053013, total testosterone level – r = 0.278921593.A relationship was found between the level of insulin after a load of 75 g of glucose and the following indicators: body weight at the birth of female respondents – r = -0.238495649, gestational term of birth – r = -0.243025226, FSH level – r = 0.291379519.Conclusions. A small positive (direct) relationship was determined between the fasting insulin level and the following indicators: WC, BMI, TSH level, and total testosterone level. An increase of these indicators is associated with an increase in fasting insulin level. A slight inverse linear relationship was found between the level of fasting insulin and the duration of menstrual function, the duration of bleeding during menstruation and the DHEA-S level.A slight inverse relationship is observed between the level of insulin after load and body weight at birth, the term of birth. Lower birth weight and early gestational age are associated with increased insulin levels after load.There is a direct relationship between post-load insulin levels and FSH levels. An increased FSH concentration will lead to a rise of insulin level after load.

Suppression of gp130 attenuated insulin-mediated signaling and glucose uptake in skeletal muscle cells

The aim of the present study was to investigate the effects of Oncostatin M receptor (OSMR) subunit gp130 knockdown on insulin-stimulated glucose metabolism-related signaling pathways and glucose uptake in skeletal muscle cells. siRNA-mediated gp130 knockdown was conducted in C2C12 muscle cells, and insulin was added and incubated for 1 h. The cells were cultivated to analyze the mRNA levels of gp130, phosphorylation of STAT3, and glucose metabolism-regulated signaling pathways, and OSM levels in the culture medium were analyzed. The phosphorylation of STAT 3 was significantly decreased in gp130−/− cell. The insulin stimulation was significantly increased in both gp130−/− and gp130+/+ and the phosphorylation of IRS-1 Ser 1101 was significantly decreased in gp130−/−. PI3-kinase activity and Akt Thr 308 phosphorylation were significantly decreased in gp130−/−. The insulin-stimulated increase in glucose uptake rate was significantly attenuated in gp130−/−. In the culture medium, OSM levels were significantly lower in gp130+/+compared to gp130−/− cell. In conclusion, the knockdown of gp130 caused a decrease in STAT 3 phosphorylation and resulted in the attenuation of insulin-mediated glucose metabolism signaling in skeletal muscle cells. Thus, an excessive increase in extracellular OSM may induce blunted insulin action in skeletal muscle cells.

Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48–0.85), 0.94 (0.72–1.23), 0.68 (0.50–0.92) and 1.62 (1.24–2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.

Effect of Swimming Exercise on Levels of Blood Glucose, Adiponectin, Glucose-6-Phosphatase and Lipid Profile in Diabetic Wistar Rats

Diabetes mellitus is a chronic metabolic condition that causes persistent hyperglycemia due to insulin action or secretion. Regular physical exercise has been reported to improve glycemia and lipid profile in diabetes. However, literature is scare on the effects of swimming exercise on the serum levels of adiponectin and glucose 6 phosphatase in Wister rats with diabetes This study therefore, investigated the effects of swimming exercise on adiponectin, glucose 6-phosphatase and lipid profile in male Wistar rats with streptozotocin-induced diabetes. This study was carried out on 25 male Wistar rats grouped into five groups (n=5/group): group 1=control, group 2=diabetes, group 3=diabetes treated with metformin, group 4=non-diabetes and swimming exercise, group 5=diabetes and swimming exercise. Animals in groups 2, 3, and 5 were induced with Streptozotocin (STZ) 50 mg/kg intraperitoneally. After 72 hours of diabetes induction, animals with a blood glucose level of ≥ 200 mg/dl were confirmed diabetics and used for the study. Group 3 animals were treated with metformin 200mg/kg giving orally for 28 days. Animals in groups 4 and 5 were subjected to swimming exercises for 5-10 minutes during the first week until they could swim freely for 30 minutes. The animals were then allowed to swim 5 days per week for 28 days. Swimming exercise for 28 days significantly reduced blood glucose, glucose-6-phosphatase (G6Ppase), Lactate dehydrogenase (LDH), Total cholesterol (TC), and Low-density lipoprotein (LDL) levels but caused significant increase in adiponectin and High-density lipoprotein (HDL) levels in diabetic rats compared with untreated diabetic rats. There was a significant decrease in triglyceride (TG) of diabetic animals caused by swimming for 28 days. This study demonstrated that swimming exercise for 28 days may help lower glucose level and improve insulin sensitivity by increasing adiponectin level and decreasing G6Pase activity in diabetic rats. Also, swimming exercise may help improve lipid profile in diabetic rats.

Elemental Profiling of Common Anti-diabetic Medicinal Plants of Swat and Peshawar Districts of Khyber Pakhtunkhwa (KPK) Province of Pakistan: An Investigation Using PIXE and ICP-OES.

The use of medicinal plants is integral to addressing liver, heart, lung, and other metabolic issues. These plants are rich in vitamins, minerals, flavonoids, and alkaloids, which collectively help in lowering intestinal glucose absorption and increasing insulin secretion by pancreatic tissues. Elemental analysis, encompassing major, minor, and trace elements, was performed on various parts (leaves, roots, and seeds) of 16 anti-diabetic medicinal plants collected from different regions of Swat and Peshawar in Khyber Pakhtunkhwa (KPK), Pakistan. This analysis utilized proton-induced X-ray emission (PIXE) and inductively coupled plasma optical emission spectroscopy (ICP-OES) techniques. Our PIXE and ICP-OES analysis revealed the presence of major (Ca, K, S, P), minor (Si, Cl), and trace (Al, Mn, Fe, Ni, Cu, Zn, Se, Cr, and Sc) elements in various parts (leaves, roots, and seeds) of the 16 anti-diabetic medicinal plants studied. Specifically, elements such as Ca, K, Cr, Cu, Mn, Zn, and Se were detected, all of which are known to contribute in maintaining normal glucose metabolism. Notably, Zn and Se are crucial trace elements for the synthesis, secretion, and action of insulin. Significant Zn concentrations were observed in ten anti-diabetic medicinal plants: Albizia lebbeck (AL), Atropa acuminata (AA), Avena fatua (AF), Citrus medica (CM), Commiphora wightii (CW), Cymbopogon citratus (CC), Daucus carota (DC), Ziziphus mauritiana (FM), Hyoscyamus niger (HN), and Martynia annua (MA), and significant Se concentrations were observed in twelve medicinal plants, i.e., Albizia lebbeck (AL), Allium sativum (AS), Atropa acuminata (AA), Avena fatua (AF), Cannabis sativa (CS), Capparis spinosa (CaS), Commiphora wightii (CW), Cymbopogon citratus (CC), Datura alba (DA), Daucus carota (DC), Ziziphus mauritiana (FM), and Hyoscyamus niger (HN). Our study's elemental analysis using PIXE and ICP-OES on various parts of 16 medicinal plants identified a significant number of useful elements. Elements such as Ca, K, S, P, Al, Si, Cl, Mn, Fe, Ni, Cu, Zn, Se, and Cr were identified and quantified. These findings support the potential use of these plants in managing diabetes and highlight the importance of elemental profiling in understanding their therapeutic properties.

Evaluasi Rasionalitas Insulin Pada Pasien Diabetes Mellitus Tipe 2 Rawat Jalan di RSUD Kota Madiun Periode 2022

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that occurs due to defects in insulin secretion, insulin action or both. Diabetes mellitus (DM) is currently a global health threat. Various epidemiological studies have shown an increase in the incidence and prevalence of DM in the world. Based on data from the profile of the East Java Health Office in 2021, it is estimated that DM patients in Madiun City rank fourth in the East Java region. . Objective: This research was conducted to determine the evaluation of the rationality of insulin in type 2 DM patients in the Outpatient Hospital of Madiun City Hospital for the period 2022. Methods: This research method is in the form of an observational research, retrospective data collection in the form of medical records of history of type 2 diabetes mellitus patients at Outpatient Hospital at RSUD Madison City. The total population in this study in the period January - December 2022 was 165 patients. Results: From the 62 type 2 DM patients who were outpatients at Madiun City Regional Hospital, it was found that 14.52% using single insulin and 12.90% used Detemir insulin. The use of the insulin combination was 85.48% and the Detemir – Aspart insulin combination was 58.06%. Conclusion: Evaluation of the rationality of insulin use showed that the correct drug was 100% and the correct dose was 93,55%.

Herbal Cellular Concentrate for Type 2 Diabetes

Diabetes is a group of metabolic disorders associated with chronic hyperglycemia in the blood due to defects in insulin secretion, insulin function, or both. Although the proper treatment of diabetes includes insulin injection continuously to maintain blood glucose levels, nowadays, there is an increasing interest in the use of alternative approaches for treating insulin resistance, and T2D Chicory significantly reduces blood sugar and glucose fluctuations, increases metabolism due to inulin in type 2 diabetes patients with excess weight. Equisetum arvense is one of the most effective plants for blood sugar, stabilizing metabolism, and hormone production. Tuberous roots are rich in inulin, enabling glucose utilization in the human body, and can potentially ameliorate insulin sensitivity in diabetic patients. Blueberry leaves improve insulin sensitivity and action. Galega officinalis lowers blood sugar levels for prediabetes and type-2 diabetes patients. Due to the side effects and temporary use of chemical drugs, herbal and natural medicines and chemical drugs are recommended for people with diabetes. However, more scientific studies are needed to confirm the effectiveness of herbal supplements in diabetes cases.

Effects of kaempherol-3-rhamnoside on metabolic enzymes and AMPK in the liver tissue of STZ-induced diabetes in mice

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. It involves disturbances in carbohydrate, fat, and protein metabolism due to defects in insulin secretion, insulin action, or both. Novel therapeutic approaches are continuously being explored to enhance metabolic control and prevent complications associated with the disease. This study investigates the therapeutic potential of kaempherol-3-rhamnoside, a flavonoid, in managing diabetes by modulating the AMP-activated protein kinase (AMPK) pathway and improving metabolic enzyme activities in streptozotocin (STZ) -induced diabetic mice. Diabetic mice were treated with varying doses of kaempherol-3-rhamnoside and/or insulin over a 28-day period. Glycolytic and gluconeogenesis enzyme activities in the liver, fasting blood glucose levels, serum insulin levels, lipid profiles and oxidative stress markers were assessed. Treatment with kaempherol-3-rhamnoside significantly improved glycolytic enzyme activities, reduced fasting blood glucose, and enhanced insulin levels compared to diabetic controls. The compound also normalized lipid profiles and reduced oxidative stress in the liver, suggesting its potential in reversing diabetic dyslipidemia and oxidative damage. Furthermore, kaempherol-3-rhamnoside activated the AMPK pathway, indicating a mechanism through which it could exert its effects. Kaempherol-3-rhamnoside exhibits promising antidiabetic properties, potentially through AMPK pathway activation and metabolic enzyme modulation. These findings support its potential use as an adjunct therapy for diabetes management. Further clinical studies are warranted to validate these results in human subjects.

A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults

Background/ObjectiveTo identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT).MethodsAdult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC).ResultsAt follow-up (median time 9.6 [inter-quartile range: 5.6–13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes.ConclusionsGlucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.Clinical Trial RegistryClinicalTrials.gov identifier : NCT00340132, NCT00339482

Differential Mitochondrial Adaptation of the Slow and Fast Skeletal Muscles by Endurance Running Exercise in Streptozotocin-Induced Diabetic Mice.

The skeletal muscle is the main organ responsible for insulin action, and glucose disposal and metabolism. Endurance and/or resistance training raises the number of mitochondria in diabetic muscles. The details of these adaptations, including mitochondrial adaptations of the slow and fast muscles in diabetes, are unclear. This study aimed to determine whether exercise training in streptozotocin (STZ)-induced mice leads to differential adaptations in the slow and fast muscles, and improving glucose clearance. Eight-week-old mice were randomly distributed into normal control (CON), diabetes (DM), and diabetes and exercise (DM+Ex) groups. In the DM and DM+Ex groups, mice received a freshly prepared STZ (100 mg/kg) intraperitoneal injection on two consecutive days. Two weeks after the injection, the mice in the groups ran on a treadmill for 60 min at 20 m/min for a week and subsequently at 25 m/min for 5 weeks (5 days/week). The analyses indicated that running training at low speed (25 m/min) enhanced mitochondrial enzyme activity and expression of lactate and glucose transporters in the plantaris (low-oxidative) muscle that improved whole-body glucose metabolism in STZ-induced diabetic mice. There were no differences in glucose transporter expression levels in the soleus (high-oxidative) muscle. The endurance running exercise at 20-25 m/min was sufficient to induce mitochondrial adaptation in the low-oxidative muscles, but not in the high-oxidative muscles, of diabetic mice. In conclusion, the present study indicated that running training at 25 m/min improved glucose metabolism by increasing the mitochondrial enzyme activity and glucose transporter 4 and monocarboxylate transporter 4 protein contents in the low-oxidative muscles in STZ-induced diabetic mice.

Harnessing androgen receptor: Revolutionizing diabetes treatment in men with selective androgen receptor modulators

Diabetes is a chronic metabolic disorder. Among different types, type 2 diabetes mellitus (T2DM) is the most prevalent accounting for 90 % to 95 % of all reported cases. T2DM is more prevalent in men compared to women. According to several literature reports, men with low testosterone levels and/or decreased androgen receptor (AR) expression are prone to T2DM. Consistently, androgen therapy was effective in treating T2DM in several preclinical and clinical studies. Activation of AR has been shown to induce the gene expression of NGN3 and NEUROD1 which helps in pancreatic β-cell differentiation, regeneration, and proliferation. AR activation can also increase the gene expression of glucose transporter (GLUT4) in the hepatocytes, skeletal muscle fibers, and adipocytes. An increase in GLUT4 expression could augment the activity of insulin and could help to reduce the insulin dose. However, testosterone therapy even for the short term was found to produce significant adverse effects. The rate-limiting being the increase in the hematocrit value. Hence, to minimize or avoid the serious adverse effects associated with androgen therapy, selective androgen receptor modulators (SARMs) could be employed to harness the goodness of the AR. A preliminary study based on the network analysis of the genes associated with T2DM has also pointed towards the importance of AR in T2DM.