Unchanged Insulin Secretion and Glucose Tolerance but Increased Insulin Clearance during Long-Term Calcium Antagonism with Felodipine in Essential Hypertension

1987 ◽  
Vol 19 (09) ◽  
pp. 426-429 ◽  
Author(s):  
P. Katzman ◽  
U. Hulthén ◽  
B. Hökfelt
Keyword(s):  
Essential Hypertension ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Clearance ◽  
Calcium Antagonism

scholarly journals Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Camila Lubaczeuski ◽  
Luciana Mateus Gonçalves ◽  
Jean Franciesco Vettorazzi ◽  
Mirian Ayumi Kurauti ◽  
Junia Carolina Santos-Silva ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Insulin Clearance ◽  
Protein Diet ◽  
Low Protein Diet ◽  
High Fat ◽  
Insulin Degrading Enzyme ◽  
Low Protein

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

scholarly journals Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises

2020 ◽  
Vol 8 (1) ◽  
pp. e001062
Author(s):  
Priyathama Vellanki ◽  
Darko Stefanovski ◽  
Isabel I Anzola ◽  
Dawn D Smiley ◽  
Limin Peng ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Carbohydrate Tolerance ◽  
Link Type ◽  
History Of

IntroductionMany African-Americans (AA) with obesity with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) discontinue insulin therapy and achieve near-normoglycemia remission (hemoglobin A1c (HbA1c) <7%, fasting blood glucose (FBG) <130 mg/dL) and able to be managed on oral antidiabetic agents (OAD) during follow-up. Using combined data from two randomized controlled trials, we assessed long-term carbohydrate tolerance and changes in insulin sensitivity and insulin secretion.Research design and methodsSeventy-five participants with DKA (n=33) and SH (n=42) underwent 2-hour 75 g oral glucose tolerance test (OGTT) after insulin discontinuation and every 6 months until hyperglycemia relapse (FBG ≥130 mg/dL, HbA1c >7% or two random BG ≥180 mg/dL) while treated with OAD (metformin, sitagliptin or pioglitazone) or placebo. Glucose tolerance status was defined as per the American Diabetes Association. Sensitivity index (Si) was calculated by oral minimal model, insulin secretion as the incremental area under the curve of insulin (IncreAUCi) and disposition index (DI) as Si×IncreAUCi.ResultsDuring remission, OGTT showed normal glucose tolerance (NGT) (n=9 (12%)), prediabetes (n=34 (45%)) and diabetes (n=32 (43%)). DI and Si were higher in patients with NGT versus prediabetes versus diabetes (p<0.001), while IncreAUCi was not significantly different among NGT, prediabetes and diabetes (p=0.14). Achieving NGT status did not prolong near-normoglycemia remission. OAD treatment significantly prolonged hyperglycemia relapse-free survival (log-rank p=0.0012) compared with placebo and was associated with lower hyperglycemia relapse (HR: 0.45, 95% CI: (0.21 to 0.96), p=0.04).ConclusionsIn AA patients with obesity with history of DKA and SH, near-normoglycemia remission is associated with improved insulin secretion and action with half of patients achieving NGT or prediabetes, and only half having diabetes on OGTT. NGT and prediabetes on OGTT were not associated with prolonged hyperglycemia relapse-free survival.Trial registration numberNCT01099618, NCT00426413.

scholarly journals Reduced insulin clearance and lower insulin-degrading enzyme expression in the liver might contribute to the thrifty phenotype of protein-restricted mice

2014 ◽  
Vol 112 (6) ◽  
pp. 900-907 ◽  
Author(s):  
Luiz F. Rezende ◽  
Rafael L. Camargo ◽  
Renato C. S. Branco ◽  
Ana P. G. Cappelli ◽  
Antonio C. Boschero ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Insulin Clearance ◽  
Protein Diet ◽  
Restricted Diet ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Thrifty Phenotype

Nutrient restriction during the early stages of life usually leads to alterations in glucose homeostasis, mainly insulin secretion and sensitivity, increasing the risk of metabolic disorders in adulthood. Despite growing evidence regarding the importance of insulin clearance during glucose homeostasis in health and disease, no information exists about this process in malnourished animals. Thus, in the present study, we aimed to determine the effect of a nutrient-restricted diet on insulin clearance using a model in which 30-d-old C57BL/6 mice were exposed to a protein-restricted diet for 14 weeks. After this period, we evaluated many metabolic variables and extracted pancreatic islet, liver, gastrocnemius muscle (GCK) and white adipose tissue samples from the control (normal-protein diet) and restricted (low-protein diet, LP) mice. Insulin concentrations were determined using RIA and protein expression and phosphorylation by Western blot analysis. The LP mice exhibited lower body weight, glycaemia, and insulinaemia, increased glucose tolerance and altered insulin dynamics after the glucose challenge. The improved glucose tolerance could partially be explained by an increase in insulin sensitivity through the phosphorylation of the insulin receptor/protein kinase B and AMP-activated protein kinase/acetyl-CoA carboxylase in the liver, whereas the changes in insulin dynamics could be attributed to reduced insulin secretion coupled with reduced insulin clearance and lower insulin-degrading enzyme (IDE) expression in the liver and GCK. In summary, protein-restricted mice not only produce and secrete less insulin, but also remove and degrade less insulin. This phenomenon has the double benefit of sparing insulin while prolonging and potentiating its effects, probably due to the lower expression of IDE in the liver, possibly with long-term consequences.

THE EFFECT OF LONG-TERM DIPHENYLHYDANTOIN THERAPY ON GLUCOSE TOLERANCE AND INSULIN SECRETION: A CONTROLLED TRIAL

1980 ◽  
Vol 12 (6) ◽  
pp. 575-580 ◽  
Author(s):  
D. A. PERRY-KEENE ◽  
R.G. LARKINS ◽  
P. HEYMA ◽  
C. T. PETER ◽  
D. ROSS ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Controlled Trial

Glucoregulatory hormone response to insulin-induced hypoglycaemia following long-term calcium antagonism with felodipine in patients with essential hypertension

1987 ◽  
Vol 116 (4) ◽  
pp. 473-478 ◽  
Author(s):  
Per L. Katzman ◽  
U. Lennart Hulthén ◽  
Bernt Hökfelt
Keyword(s):  
Essential Hypertension ◽  
Insulin Injection ◽  
Serum Levels ◽  
Term Treatment ◽  
Hormone Response ◽  
Who Grade ◽  
Calcium Antagonism ◽  
Long Term Treatment ◽  
Basal Plasma

Abstract. The effect of 8 weeks' treatment with the dihydropyridine calcium antagonist felodipine on glucoregulatory hormone response following insulin-induced hypoglycaemia was evaluated in 7 patients with essential hypertension, WHO grade I–II. After an iv insulin injection (0.1 IU/kg), blood glucose decrement and nadir were similar before and during felodipine treatment. Basal glucagon, noradrenaline, adrenaline, GH and cortisol levels were unchanged, and the response to insulin-induced hypoglycaemia was similar before and during felodipine treatment. Basal plasma dopamine levels were similar and did not change during insulin-induced hypoglycaemia before and during felodipine treatment. Basal serum levels of TSH, T3 and T4 were unaltered following felodipine. In conclusion, long-term treatment with felodipine did not alter the hypoglycaemic effect of exogenous insulin, or the recovery from hypoglycaemia or the glucoregulatory hormone response to insulin-induced hypoglycaemia in patients with essential hypertension.

Sign in / Sign up

Export Citation Format

Share Document