Enhancing ß-cell function and identity in type 2 diabetes: The protective role of Coptis deltoidea C. Y. Cheng et Hsiao via glucose metabolism modulation and AMPK signaling activation.

BACKGROUND: Abnormalities in glucose metabolism may be the underlying cause of ß-cell dysfunction and identity impairment resulting from high glucose exposure. In China, Coptis deltoidea C. Y. Cheng et Hsiao (YL) has demonstrated remarkable hypoglycemic effects. HYPOTHESIS/PURPOSE: To investigate the hypoglycemic effect of YL and determine the mechanism of YL in treating diabetes. METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of YL. YL was administrated once daily for 8 weeks. The hypoglycemic effect of YL was assessed by fasting blood glucose, an oral glucose tolerance test, insulin levels, and other indexes. The underlying mechanism of YL was examined by targeting glucose metabolomics, western blotting, and qRT-PCR. Subsequently, the binding capacity between predicted AMP-activated protein kinase (AMPK) and important components of YL (Cop, Ber, and Epi) were validated by molecular docking and surface plasmon resonance. Then, in AMPK knockdown MIN6 cells, the mechanisms of Cop, Ber, and Epi were inversely confirmed through evaluations encompassing glucose-stimulated insulin secretion, markers indicative of ß-cell identity, and the examination of glycolytic genes and products. RESULTS: YL (0.9 g/kg) treatment exerted notable hypoglycemic effects and protected the structural integrity and identity of pancreatic ß-cells. Metabolomic analysis revealed that YL inhibited the hyperactivated glycolysis pathway in diabetic mice, thereby regulating the products of the tricarboxylic acid cycle. KEGG enrichment revealed the intimate relationship of this process with the AMPK signaling pathway. Cop, Ber, and Epi in YL displayed high binding affinities for AMPK protein. These compounds played a pivotal role in preserving the identity of pancreatic ß-cells and amplifying insulin secretion. The mechanism underlying this process involved inhibition of glucose uptake, lowering intracellular lactate levels, and elevating acetyl coenzyme A and ATP levels through AMPK signaling. The use of a glycolytic inhibitor corroborated that attenuation of glycolysis restored ß-cell identity and function. CONCLUSION: YL demonstrates significant hypoglycemic efficacy. We elucidated the potential mechanisms underlying the protective effects of YL and its active constituents on ß-cell function and identity by observing glucose metabolism processes in pancreatic tissue and cells. In this intricate process, AMPK plays a pivotal regulatory role.

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

A prospective guide for clinical implementation of selected OGTT- derived surrogate indices for the evaluation of ß- cell function and insulin sensitivity in patients with transfusion-dependent ß- thalassaemia.

The gold standard for the measurement of insulin secretion is the hyperglycemic clamp and for insulin sensitivity the hyperinsulinemic euglycemic clamp, respectively. A number of surrogate indices, derived from plasma glucose and insulin levels at a fasting state or after oral glucose load, have been proposed to estimate ß-cell response, and the ability of ß-cells to compensate for changes of insulin sensitivity by modulating insulin secretion (disposition index). Starting from the current recommendations for the annual screening of glucose dysregulation in patients with transfusion dependent ß-thalassemia (ß-TDT), this article summarizes the most frequently used indirect indices of insulin secretion and resistance derived from the oral glucose tolerance test (OGTT) and discusses the strengths and weaknesses of selected indices and the basic concepts underlying each method for the appropriate evaluation of glucose regulation. Basal indices for ß-cell function and insulin sensitivity, albeit simple and cheap, have limited usefulness due to a high coefficient variation and the lack of data about response to glucose load. Therefore, measurement of indices during an OGTT, despite being costly and time-consuming, is suggested since it can detect, even subtle, dynamic changes in insulin secretion and glucose handling. In patients with ß-TDT, the indices derived from OGTT may offer an additional factor to evaluate the efficiency of iron chelation therapy and detect patients who may need intensification of iron chelation therapy and/or pharmacological intervention.

Oral Glucose Tolerance Test (OGTT) Evidence for the Postprandial Anti-Hyperglycemic Property of Salacca zalacca (Gaertn.) Voss Seed Extract.

Salak seed extract (Salacca zalacca) is known for its high antioxidant content and low caffeine levels, making it a promising candidate for the development of value-added health products. However, there is a lack of scientific evidence for its anti-hyperglycemic effects. To address this, we investigated the in vitro and in vivo anti-hyperglycemic and antioxidant effects of salak seed extract. The HPLC chromatogram of salak seed extract shows a prominent peak that corresponds to chlorogenic acid. In vitro studies revealed that salak seeds inhibited α-glucosidase activity and glucose uptake in Caco-2 cells in a concentration-dependent manner, while also exhibiting antioxidant properties. The extract exhibits a non-competitive inhibition on α-glucosidase activity, with an IC50 and Ki of 16.28 ± 7.22 and 24.81 µg/mL, respectively. In vivo studies utilizing streptozotocin-nicotinamide-induced diabetic mice showed that the extract significantly reduced fasting blood glucose (FBG) levels in the oral glucose tolerance test. Continuous administration of the salak seed extract resulted in lower FBG levels by 13.8% as compared with untreated diabetic mice, although this change was not statistically significant. The estimated LD50 value of salak seed extract exceeds 2000 mg/kg, and no toxicity symptoms have been detected. Our research supports that salak seed extract has the potential to serve as a functional food or supplement that may be beneficial in reducing postprandial hyperglycemia among people with type 2 diabetes. This effect was explained by the salak's inhibitory mechanisms of glucose absorption due to inhibition of both α-glucosidase activity and intestinal glucose uptake, coupled with its antioxidant effects.

Gestational Vitamin E Status and Gestational Diabetes Mellitus: A Retrospective Cohort Study.

OBJECTIVES: To examine the association between vitamin E (VE) status and gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted by using data of 52,791 women at 137 hospitals across 22 provinces of China. A fasting plasma glucose (FPG) level of ≥5.1 mmol/L between the 24th and 40th weeks of gestation was used as the criteria for the diagnosis of GDM. Mean FPG level and GDM rate were calculated within each combination of the first-trimester VE concentration categories and gestational change categories. The associations of the first-trimester VE concentrations and gestational VE change with FPG and GDM were examined by employing generalized additive models (GAMs). RESULTS: 7162 (13.57%) cases were diagnosed with GDM. The GDM rate was 22.44%, 11.50%, 13.41%, 12.87%, 13.17%, 13.44%, 12.64%, and 14.24% among women with the first-trimester VE concentrations of <7.2, 7.2-7.9, 8.0-9.3, 9.4-11.0, 11.1-13.2, 13.3-15.8, 15.9-17.7, and 17.8-35.9 mg/L, respectively. The GDM rate was 15.96%, 13.10%, 13.64%, and 12.87% among women with gestational VE change of <0, 0-0.19, 0.20-0.29, ≥0.30 mg/L per week, respectively. Multivariable adjusted GAM analyses found that the first-trimester VE concentration was associated with the FPG levels and GDM risk in an L-shaped pattern; the FPG levels and GDM risk decreased sharply to a threshold (around 7 mg/L), and then were keep flat. Gestational VE decreases when the first-trimester VE level was less than 11 mg/L were related to increased FPG levels and GDM risk. CONCLUSIONS: Both low first-trimester VE levels and subsequent gestational VE decrease were related with increased risk of GDM. The findings suggest the necessity of having VE-rich foods and appropriate VE supplementation to prevent GDM for pregnant women with low baseline VE levels.

Oral administration of wild plant-derived minerals and red ginseng ameliorates insulin resistance in fish through different pathways.

Many kinds of fish are characterized by a limited efficiency to use carbohydrates. For this reason, raw fish and mixed feed containing a lot of fish meal have been used as feed for fish farming. However, continuing to use high-protein diets not only increases the cost of fish farming, but may also fuel animal protein shortages. Furthermore, carbohydrates are added to improve the texture of the feed and act as a binding agent and are usually contained at 20% in the feed. It makes sense, therefore, to find ways to make good use of carbohydrates rather than wasting them. The physiological mechanisms of glucose intolerance in fish are not yet well understood. Therefore, we investigated the glucose utilization of fish, omnivorous goldfish Carassius auratus and carnivorous rainbow trout Oncorhynchus mykiss. Furthermore, the effects of oral administration of wild plant-derived minerals and red ginseng on the glucose utilization in these fish muscle cells were investigated. As a result, we found the following. (1) An extremely high insulin resistance in fish muscle and the symptom was more pronounced in carnivorous rainbow trout. (2) Administration of wild plant-derived minerals promotes the translocation of the insulin-responsive glucose transporter GLUT4 to the cell surface of white muscle via activation of the PI3 kinase axis, whereas administration of red ginseng not only promotes GLUT4 transfer and translocation to the cell surface of white muscle via AMPK activation as well as promoting glucose uptake into muscle cells via a pathway separate from the insulin signaling system. (3) In fish, at least goldfish and rainbow trout, both PI3K/Akt and AMPK signaling cascades exist to promote glucose uptake into muscle cells, as in mammals.

Evaluation of anti-inflammatory, diuretic and oral glucose tolerance activities of phenolic compound-rich fractions of Hammada articulata in Albino Wistar rats.

Hammada articulata is a plant widely used by the locals of the Algerian Sahara for multiple medicinal purposes. However, little was known about its chemical composition and the mechanisms of its bioactivity. For this purpose, the derived extracts [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 80% ethanol extract of its aerial parts, were evaluated for their anti-inflammatory, diuretic, and anti-hyperglycemic activities in vivo. A preliminary phytochemical screening of H. articulata extracts showed the presence of a variety of secondary metabolites. RP-HPLC/DAD was used to analyze some fractions obtained by fractionation of the three derived extracts, by column chromatography and chosen because of the abundance and simplicity of their chemical composition. The fractions obtained from EtOAc and n-BuOH extracts showed a particular richness in phenolic compounds mainly naringenin, quercetin, kaempferol, myricetin, and rutin, which were known for their many interesting biological activities. The three derived extracts from H. articulata were assessed for their anti-inflammatory activity in the carrageenan-induced edema model in rats and their diuretic activity using hydrochlorothiazide (HCTZ) as a diuretic reference. All extracts showed considerable anti-inflammatory activity; the highest was registered in the group treated with the n-BuOH extract. However, for the diuretic activity, only the chloroform extract was active, with a diuretic spectrum similar to that of the standard diuretic HCTZ. The anti-hyperglycemic effect was carried out on the three derived extracts administered orally at a dose of 200 mg/kg, using the glucose tolerance test after gavage with the extracts. The EtOAc and n-BuOH extracts showed significant anti-hyperglycemic activity, improving oral glucose tolerance in normal rats.

Comparing the effects of water temperature and additives in glucose solution on pregnant women's taste, side effects, and glycemic levels during an oral glucose tolerance test: a randomized controlled trial.

BACKGROUND: The oral glucose tolerance test is a common method of diagnosing gestational diabetes mellitus. This test causes several unpleasant side effects such as nausea, vomiting, abdominal bloating, and headache. OBJECTIVE: This study aimed to assess the effect of liquid temperature and additives on pregnant women's taste perception, side effects, and glycemic levels in an oral glucose tolerance test. STUDY DESIGN: This study was a single-center, randomized, and multi- and open-arm clinical trial. A total of 399 participants receiving the 75-g oral glucose tolerance test for gestational diabetes mellitus diagnosis were included. Solutions for use in the 75-g oral glucose tolerance test were prepared in 8 formulas, with the participants randomly assigned to 1 of the 8 groups: room-temperature water, hot water, cold water, hot water with tea bag, room-temperature water with tea bag, cold water with tea bag, room-temperature soda water, and cold soda water. The main study outcomes were glycemic levels, satisfaction, perceived taste, side effects, and gestational diabetes mellitus. Glycemic levels were measured when fasted and at 1 hour and 2 hours after glucose administration. Satisfaction, taste perception, and side effects were evaluated immediately after the oral glucose tolerance test, and gestational diabetes mellitus was determined on the basis of glycemic levels. RESULTS: The cold soda water solution led to a significantly higher glycemic level at 1 hour after glucose intake compared with room-temperature soda water solution (P=.009). Glucose formula was found to not significantly affect gestational diabetes mellitus incidence (P>.05) or the participants' satisfaction, vomiting, headache, or abdominal bloating (P>.05). However, the formula did significantly affect perceived taste (P=.027) and the degree of nausea (P=.014). CONCLUSION: Several glucose solutions, such as cold glucose solution and any-temperature glucose solution containing a tea bag, led to slightly higher taste scores and a lower degree of nausea compared with the room-temperature water-based glucose solution. However, soda water was found to affect the glycemic level at 1 hour after glucose intake, and is not suggested for use for gestational diabetes mellitus diagnosis.

Antihyperglycemic activity of nanoemulsion of brown algae (Sargassum sp.). Ethanol extract in glucose tolerance test in male mice.

Nanoemulsion technology has been widely developed and applied to extracts of natural materials to enhance bioavailability and medicinal effects. This study aimed to determine the effectiveness of the Sargassum sp. ethanol extract nanoemulsions as an antihyperglycemic agent against fasting blood glucose levels in mice. The nanoemulsion formulation used Sargassum sp. extract and some additional ingredients, including chitosan, sodium tripolyphosphate, and tween 80. The antihyperglycemic test consisted of four groups, which were randomly selected. Treatment group (I) was given a nanoemulsion base without algae extract with a volume of 0.2mL/20gramBW; treatment group (II) was given glibenclamide at a dose of 0.52mg/20gramBW in 0.5% carboxymethylcellulose sodium (NaCMC) suspension with a volume of 0.2mL/20gramBW; treatment group (III) was given Sargassum sp. ethanol extract at a dose of 0.66mg/20 gramBW in 0.5% Na CMC suspension with a volume of 0.2mL/20gramBW; the treatment group (IV) was given formula of nanoemulsions of ethanol extract Sargassum sp with a volume of 0.2mL/20gramBW equivalent to a dose concentration Sargassum sp. ethanol extract of 0.66mg/20gramBW. The size of the nanoemulsion particles of the Sargassum sp. extract was 341.5-296.5nm with a zeta potential of 19.4-16.9mv. Treatment group (II) had the same antihyperglycemic effect as treatment group (IV). In contrast, treatment groups (I) and (III) had a relatively lower antihyperglycemic effect. This suggests that the Sargassum sp. extract nanoemulsion formula can be used as an alternative antihyperglycemic agent.

Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA.

INTRODUCTION: Clinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS: Within the context of Gestational Diabetes' Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974). RESULTS: Overall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67)). CONCLUSIONS: Guideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care.

Effect of dietary n-6: n-3 Poly-Unsaturated fatty acids ratio on gestational diabetes mellitus: a prospective cohort.

OBJECTIVE: The aim of this study was to investigate the relationship between dietary n-6: n-3 poly-unsaturated fatty acids (PUFA) ratio and the risk of developing gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 100 pregnant women were prospectively included for detailed information on dietary intake at 16-18 weeks evaluated using a three-day food record, and subsequent GDM diagnosis at 24-28 weeks. Participants were divided into two groups for analysis: GDM group (n = 22) and control group (n = 78) based on oral glucose tolerance test results performed between 24 and 28 weeks. RESULTS: The average dietary n-6: n-3 PUFA ratio in the control group was 5.63 ± 2.12 and that in the GDM group was 8.35 ± 3.45, within a significant difference (p < .05). A significant difference was associated with a higher dietary n-6: n-3 PUFA ratio and GDM (adjusted odds ratio = 4.29, 95%confidence interval:1.303, 14.124). CONCLUSIONS: Higher dietary n-6: n-3 PUFA ratio was associated with higher odds of GDM. Given the small sample, further studies are required to confirm this hypothesis.

Hyperbaric oxygen treatment improves pancreatic ß­cell function and hepatic gluconeogenesis in STZ­induced type­2 diabetes mellitus model mice.

Type­2 diabetes mellitus (T2DM) causes several complications that affect the quality of life and life span of patients. Hyperbaric oxygen therapy (HBOT) has been used to successfully treat several diseases, including carbon monoxide poisoning, ischemia, infections and diabetic foot ulcer, and increases insulin sensitivity in T2DM. The present study aimed to determine the effect of HBOT on ß­cell function and hepatic gluconeogenesis in streptozotocin (STZ)­induced type­2 diabetic mice. To establish a T2DM model, 7­week­old male C57BL/6J mice were fed a high­fat diet (HFD) and injected once daily with low­dose STZ for 3 days after 1­week HFD feeding. At the 14th week, HFD+HBOT and T2DM+HBOT groups received 1­h HBOT (2 ATA; 100% pure O2) daily from 5:00 to 6:00 p.m. for 7 days. The HFD and T2DM groups were maintained under normobaric oxygen conditions and used as controls. During HBOT, the 12­h nocturnal food intake and body weight were measured daily. Moreover, blood glucose was measured by using a tail vein prick and a glucometer. After the final HBO treatment, all mice were sacrificed to conduct molecular biology experiments. Fasting insulin levels of blood samples of sacrificed mice were measured by an ultrasensitive ELISA kit. Pancreas and liver tissues were stained with hematoxylin and eosin, while immunohistochemistry was performed to determine the effects of HBOT on insulin resistance. TUNEL was used to determine the effects of HBOT on ß­cell apoptosis, and immunoblotting was conducted to determine the ß­cell apoptosis pathway. HBOT notably reduced fasting blood glucose and improved insulin sensitivity in T2DM mice. After HBOT, ß­cell area and ß­cell mass in T2DM mice were significantly increased. HBOT significantly decreased the ß­cell apoptotic rate in T2DM mice via the pancreatic Bcl­2/caspase­3/poly(ADP­ribose) polymerase (PARP) apoptosis pathway. Moreover, HBOT improved the morphology of the liver tissue and increased hepatic glycogen storage in T2DM mice. These findings suggested that HBOT ameliorated the insulin sensitivity of T2DM mice by decreasing the ß­cell apoptotic rate via the pancreatic Bcl­2/caspase­3/PARP apoptosis pathway.

Insulin treatment of patients with gestational diabetes: does dosage play a role?

BACKGROUND AND OBJECTIVE: In nonpregnant patients high insulin requirements are associated with hypoglycemia and weight gain but not with improvement in glucose control. The effect of insulin requirement on maternal and neonatal outcomes in gestational diabetes mellitus (GDM) is yet unknown. METHODS: We conducted a retrospective cohort study of maternal and neonatal outcomes of pregnancy according to insulin requirements in women with GDM who were followed and delivered at the Yitzhak Shamir Medical Center between 2006 and 2016. The daily insulin dose in units per body weight was divided into quartiles and analyses were performed to compare the lowest, highest, and two middle quartiles. The primary outcome was a composite of any of the following: cesarean-section (CS), preeclampsia, macrosomia and large for gestational age (LGA) birth weight, neonatal intensive care unit admission, need for phototherapy, and neonatal hypoglycemia. RESULTS: Women were divided according to their insulin requirements as follows: 79 (24.8%) women who needed <0.13 IU/kg/day of insulin (insulin-sensitive group), 160 (50%) women who needed 0.14-0.42 IU/kg/day of insulin (comparison-group), and the rest who needed >0.43 IU/kg/day of insulin (insulin resistant group). There were no differences in the composite outcome between the groups (64.6, 61.3, and 69.6% for the insulin sensitive-, comparison- and resistant- groups, respectively, p = .44). Women in the insulin-resistant group had higher fasting glucose levels in the first trimester (91, 98 and 102 mg/dL for women in the insulin sensitive-, comparison- and insulin-resistant groups, respectively; p = .01). Women in the insulin-sensitive group had significantly better glycemic control (fasting glucose levels ≤90 mg/dL and 1-hour and 2-hour postprandial glucose levels ≤140 mg/dL and ≤120 mg/dL for more than 80% of measurements) than those in the insulin-resistant group (70.3 versus 29.9%; p < .001). The rate of CS was significantly higher in the insulin-resistant group (42.3 versus 24.1%; p = .03), but the rate of LGA birth weight was surprisingly higher in the insulin-sensitive group (29.5 versus 16.7%, p = .04). After controlling for confounders, women in the insulin-sensitive group had a decreased risk for CS in relation to the comparison group (OR = 0.46, 95%CI 0.23-0.9, p = .025). CONCLUSION: We found no association between insulin requirements and adverse composite outcome in women with GDM. However, those with higher insulin requirements have poorer glucose control and higher rates of CS than those with lower insulin requirements. Larger studies are needed to inquire short- and long-term outcomes of insulin requirements on fetal and maternal outcomes.

Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes.

CONTEXT: Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on ß-cell function remain unclear. OBJECTIVE: To investigate the effects of vitamin D3 supplementation on insulin sensitivity and ß-cell function. METHODS: This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months. MAIN OUTCOME: Disposition index (DI), as an estimate of ß-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT). RESULTS: Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level <12 ng/mL, the mean percent differences for DI between the vitamin D and placebo groups was 8.5 (95% CI, 0.2-16.8). CONCLUSIONS: Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of ß-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination.

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.

Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium.

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipid concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after 2 mo of long-term SD, the intravenous glucose tolerance test showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, 1 mo of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.NEW & NOTEWORTHY Our findings demonstrated that long-term sleep deprivation is closely associated with metabolic syndromes. Bifidobacterium administration showed a superior effect on insulin resistance caused by sleep deprivation. Overall, we provide prevention and treatment methods for long-term sleep deprivation, a bad lifestyle habit among specific occupational practitioners, such as irregular shift workers.

Efficacy of Cyanotis tuberosa (Roxb.) Schult. &Schult. f. root tubers' active fraction as anti-diabetic, antihyperlipidemic and antioxidant in Streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyanotis tuberosa (Roxb.) Schult. &Schult.f. is traditionally used as ethnomedicine for curing several ailments like diabetes, liver problems, ulcers, etc. OBJECTIVE: The present study was designed to evaluate the anti-diabetic potential of Cyanotis tuberosa root tubers (CTRT)in Streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: Anti-hyperglycemic activity of hexane extract of CTRT was investigated in diabetic rats. Silica gel chromatography was used to fractionate the hexane extract and the fraction's antihyperglycemic activity was checked in diabetic rats. Effects of long-term (30 days) treatment with an active fraction (CTAF) were evaluated in diabetic rats for 30 days by measurement of body weights, glycemic control, insulin levels, HbA1c, and serum and tissue lipid profiles. Lipid peroxide levels and antioxidant status were measured in the liver and kidney. Hepatic and Renal functional markers were also measured. Phytochemical characterization of CTAF was carried out by LC-ESI-MS/MS analysis. RESULTS: Hexane extract of CTRT at a dose of 750 mg/kg b.w produced significant antihyperglycemic activity in diabetic rats whereas CTAF has produced maximum antihyperglycemic activity at the dose of 75 mg/kg b.w. Following long-term treatment with CTAF in diabetic rats, significant improvement in glycemic control, (HbA1c) along with decreased insulin resistance (HOMA-IR), increase in body weights, and plasma insulin were observed. Also, CTAF ameliorated the serum and tissue lipid profiles. In addition, CTAF suppressed lipid peroxidation and restored the activities of antioxidant enzymes in the liver and kidney to normal levels. Further, CTAF reversed the liver and kidney functional markers to normalcy. LC-ESI-MS/MS analysis revealed the presence of 7 different phytoconstituents. CONCLUSION: This study confirmed that CTAF exerts antidiabetic effects in diabetic rats by improving insulin secretion, glycemic control, and restoring functional activities of the liver and kidney. Our results suggest that root tubers of Cyanotis tuberosa can be used as a complementary or alternative agent for the treatment of diabetes mellitus.

Citrus reticulatae pericarpium Extract Decreases the Susceptibility to HFD-Induced Glycolipid Metabolism Disorder in Mice Exposed to Azithromycin in Early Life.

Background: Studies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process. Purpose: The study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated. Methods and Results: Three-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects. Conclusion: Taken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.