scholarly journals Berberine is an insulin secretagogue targeting the KCNH6 potassium channel

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Jing Lu ◽  
Sen Li ◽  
Hao Wang ◽  
Xi Cao ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Serum Insulin ◽  
Phase 1 ◽  
Chinese Herb ◽  
Underlying Mechanism ◽  
Placebo Treatment ◽  
Double Blind ◽  
Insulin Secretagogue ◽  
Beneficial Effects ◽  
Hyperglycemic Clamp

AbstractCoptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.

scholarly journals Insulin Secretion and Clearance after Subacute Estradiol Administration in Postmenopausal Women

2008 ◽  
Vol 93 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Rachael E. Van Pelt ◽  
Robert S. Schwartz ◽  
Wendy M. Kohrt
Keyword(s):  
Insulin Secretion ◽  
Postmenopausal Women ◽  
Serum Insulin ◽  
Area Under The Curve ◽  
Glucose Disposal ◽  
Molar Ratio ◽  
Inverse Association ◽  
Hyperglycemic Clamp ◽  
Increase Glucose Uptake ◽  
Strong Inverse Association

Abstract Context: Data from large clinical trials of postmenopausal women suggest that the incidence of diabetes is reduced in women randomized to estrogen-based hormone therapy when compared with placebo. Whether this is due to an effect of estrogen on insulin or glucose metabolism remains unclear. Objective: Our objective was to test the hypothesis that estradiol (E2) increases insulin secretion and clearance. Design: Serum insulin and C-peptide (CPEP) responses to hyperglycemia (250 mg/dl) plus iv l-arginine were measured on 2 separate days, with (EST) and without [control (CON)] subacute (24 h) transdermal E2 administration. Study Participants: There were 11 postmenopausal women (mean ± sd; 55 ± 4 yr) included in this study. Main Outcomes: Insulin secretion and clearance were estimated from the CPEP area under the curve and the molar ratio of CPEP to insulin area under the curve, respectively. Mean glucose disposal rate (GDR) was estimated from the rate of glucose infusion during the final 30 min of the hyperglycemic clamp. Results: There were no differences in insulin secretion or clearance between the EST and CON days. Fasting glucose was lower on the EST compared with the CON (93 ± 6 vs. 98 ± 8 mg/dl), but mean GDR was not different. However, when one outlier was excluded from analysis, GDR was increased after EST compared with CON. Furthermore, a strong inverse association was observed between years since menopause and E2-mediated changes in GDR (r = −0.794; P = 0.004). Conclusions: Contrary to our hypothesis, 24-h transdermal E2 administration did not alter insulin secretion or clearance in postmenopausal women. However, a longer time since menopause was associated with a reduced effect of E2 to increase glucose uptake.

scholarly journals Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia miltiorrhizaandPueraria lobata) in High-Risk Hypertension

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
K. S. Woo ◽  
Thomas W. C. Yip ◽  
Ping Chook ◽  
S. K. Kwong ◽  
C. C. Szeto ◽  
...  
Keyword(s):  
High Risk ◽  
Herbal Medicines ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Placebo Treatment ◽  
Left Ventricular ◽  
Adjunctive Treatment ◽  
Protective Effects ◽  
Double Blind ◽  
Beneficial Effects

Introduction. Hypertension in association with diabetes (DM), renal impairment (RI), and left ventricular hypertrophy (LVH) increases the risk of future cardiovascular events. We hypothesize, traditional herbal medicines Danshen and Gegen (D&G) have beneficial effects on atherogenesis in these high-risk hypertensive subjects.Subjects and Methods. 90 asymptomatic hypertensive subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. All data were analyzed using the Statistical Package for Social Sciences in Windows 16.0.Results. Their mean age was55±8years, and 74.4% were male. After 12 months of adjunctive therapies and compared with baseline, there were no significant changes in blood pressure, heart rate, hematological, glucose, and creatinine profiles in both placebo and D&G groups. FMD improved significantly during D&G (P=0.0001) and less so after placebo treatment (P=0.001). There was a mild but significant decrease in carotid IMT after D&G (P<0.001) but no significant changes after placebo. A trend of better improvement in FMD after higher versus lower D&G dosages was seen. D&G were well tolerated, with no significant adverse events or blood biochemistry changes.Conclusion. D&G adjunctive treatment was well tolerated and significantly improved atherogenesis in high-risk hypertensive patients, with potential in primary atherosclerosis prevention.

Magnesium–zinc–calcium–vitamin D co-supplementation improves glycemic control and markers of cardiometabolic risk in gestational diabetes: a randomized, double-blind, placebo-controlled trial

2018 ◽  
Vol 43 (6) ◽  
pp. 565-570 ◽  
Author(s):  
Maryam Karamali ◽  
Shahla Bahramimoghadam ◽  
Fateme Sharifzadeh ◽  
Zatollah Asemi
Keyword(s):  
Vitamin D ◽  
Glycemic Control ◽  
Gestational Diabetes ◽  
Cardiometabolic Risk ◽  
Serum Insulin ◽  
Controlled Trial ◽  
Double Blind ◽  
Serum Triglycerides ◽  
Double Blind Placebo ◽  
Beneficial Effects

To the best our knowledge, data on the effects of magnesium–zinc–calcium–vitamin D co-supplementation on glycemic control and markers of cardiometabolic risk in gestational diabetes mellitus (GDM) are scarce. The purpose of this study was to establish the effects of magnesium–zinc–calcium–vitamin D co-supplementation on glycemic control and markers of cardiometabolic risk of GDM patients. Sixty patients with GDM, aged 18–40 years, were randomized into 2 groups to intake either magnesium–zinc–calcium–vitamin D co-supplements or placebo (n = 30 each group) for 6 weeks in a randomized, double-blind, placebo-controlled trial. Fasting blood samples were taken at baseline and week 6 to quantify related markers. After the 6-week intervention, compared with the placebo, magnesium–zinc–calcium–vitamin D co-supplementation resulted in significant reductions in fasting plasma glucose (−0.37 ± 0.09 vs. +0.01 ± 0.09 mmol/L, P = 0.003), serum insulin levels (−21.0 ± 4.8 vs. +7.2 ± 4.8 pmol/L, P < 0.001), homeostatic model of assessment for insulin resistance (−1.0 ± 1.1 vs. +0.3 ± 1.3, P < 0.001), and a significant increase in quantitative insulin sensitivity check index (+0.02 ± 0.03 vs. −0.002 ± 0.03, P = 0.003). In addition, magnesium–zinc–calcium–vitamin D co-supplementation significantly decreased serum triglycerides (−0.25 ± 0.10 vs. +0.34 ± 0.10 mmol/L, P = 0.001) and very-low-density–cholesterol concentrations (−0.11 ± 0.04 vs. +0.15 ± 0.04 mmol/L, P = 0.001) compared with the placebo. Overall, the results of this study demonstrated that magnesium–zinc–calcium–vitamin D co-supplementation for 6 weeks among patients with GDM had beneficial effects on glycemic control and few markers of cardiometabolic risk.

Stimulation of residual insulin secretion by glibenclamide in insulin dependent diabetics

1980 ◽  
Vol 95 (3) ◽  
pp. 372-375 ◽  
Author(s):  
B. J. Burke ◽  
R. J. Sherriff
Keyword(s):  
Insulin Secretion ◽  
Insulin Therapy ◽  
Metabolic Control ◽  
C Peptide ◽  
Beneficial Effects ◽  
Insulin Dependent ◽  
Serum And Urine ◽  
Stimulation Of

Abstract. Residual insulin secretion, reflected by the presence of C-peptide in serum and urine, has been demonstrated in 5 of 10 insulin-requiring diabetics of less than 10 years' duration tested. The C-peptide response, in the C-peptide secretors, showed a significant increase in both serum and urine after 4 weeks' treatment with 15 mg glibenclamide daily in addition to their usual insulin regime although no beneficial effects in metabolic control were detected. It is suggested that glibenclamide might be a useful adjunct to insulin therapy in insulinrequiring diabetics who still secrete C-peptide.

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