scholarly journals Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nayara Carvalho Leite ◽  
Flávia de Paula ◽  
Patrícia Cristine Borck ◽  
Jean Franciesco Vettorazzi ◽  
Renato Chaves Souto Branco ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Malnutrition ◽  
Obese Mice ◽  
Amplifying Pathway

scholarly journals The Capacity to Secrete Insulin Is Dose-Dependent to Extremely High Glucose Concentrations: A Key Role for Adenylyl Cyclase

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 401
Author(s):  
Katherine M. Gerber ◽  
Nicholas B. Whitticar ◽  
Daniel R. Rochester ◽  
Kathryn L. Corbin ◽  
William J. Koch ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Adenylyl Cyclase ◽  
Human Islets ◽  
Adenylyl Cyclase Activity ◽  
World Record ◽  
Glucokinase Activator ◽  
Amplifying Pathway ◽  
Dose Dependent ◽  
Adenylyl Cyclase Inhibitor ◽  
Cyclase Activator

Insulin secretion is widely thought to be maximally stimulated in glucose concentrations of 16.7-to-30 mM (300-to-540 mg/dL). However, insulin secretion is seldom tested in hyperglycemia exceeding these levels despite the Guinness World Record being 147.6 mM (2656 mg/dL). We investigated how islets respond to 1-h exposure to glucose approaching this record. Insulin secretion from human islets at 12 mM glucose intervals dose-dependently increased until at least 72 mM glucose. Murine islets in 84 mM glucose secreted nearly double the insulin as in 24 mM (p < 0.001). Intracellular calcium was maximally stimulated in 24 mM glucose despite a further doubling of insulin secretion in higher glucose, implying that insulin secretion above 24 mM occurs through amplifying pathway(s). Increased osmolarity of 425-mOsm had no effect on insulin secretion (1-h exposure) or viability (48-h exposure) in murine islets. Murine islets in 24 mM glucose treated with a glucokinase activator secreted as much insulin as islets in 84 mM glucose, indicating that glycolytic capacity exists above 24 mM. Using an incretin mimetic and an adenylyl cyclase activator in 24 mM glucose enhanced insulin secretion above that observed in 84 mM glucose while adenylyl cyclase inhibitor reduced stimulatory effects. These results highlight the underestimated ability of islets to secrete insulin proportionally to extreme hyperglycemia through adenylyl cyclase activity.

Metabolic amplifying pathway increases both phases of insulin secretion independently of β-cell actin microfilaments

2010 ◽  
Vol 299 (2) ◽  
pp. C389-C398 ◽  
Author(s):  
Nizar I. Mourad ◽  
Myriam Nenquin ◽  
Jean-Claude Henquin
Keyword(s):  
Insulin Secretion ◽  
Actin Polymerization ◽  
Second Phase ◽  
Actin Microfilaments ◽  
Actin Depolymerization ◽  
Inhibitory Function ◽  
Insulin Granules ◽  
Priming Process ◽  
Underlying Mechanisms ◽  
Amplifying Pathway

Two pathways control glucose-induced insulin secretion (IS) by β-cells. The triggering pathway involves ATP-sensitive potassium (KATP) channel-dependent depolarization, Ca2+ influx, and a rise in the cytosolic Ca2+ concentration ([Ca2+]c), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca2+]c. The underlying mechanisms are unknown. Here, we tested the hypothesis that amplification implicates actin microfilaments. Mouse islets were treated with latrunculin B and cytochalasin B to depolymerize actin or jasplakinolide to polymerize actin. They were then perifused to measure [Ca2+]c and IS. Metabolic amplification was studied during imposed steady elevation of [Ca2+]c by tolbutamide or KCl or by comparing the magnitude of [Ca2+]c and IS changes produced by glucose and tolbutamide. Both actin polymerization and depolymerization augmented IS triggered by all stimuli without increasing (sometimes decreasing) [Ca2+]c, which indicates a predominantly inhibitory function of microfilaments in exocytosis at a step distal to [Ca2+]c increase. When [Ca2+]c was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was facilitated by actin depolymerization and unaffected by polymerization. Both phases of IS were larger in response to high-glucose than to tolbutamide in low-glucose, although triggering [Ca2+]c was lower. This difference in IS, due to amplification, persisted when the IS rate was doubled by actin depolymerization or polymerization. In conclusion, metabolic amplification is rapid and influences the first as well as the second phase of IS. It is a late step of stimulus-secretion coupling, which does not require functional actin microfilaments and could correspond to acceleration of the priming process conferring release competence to insulin granules.

Insulin secretion and carbohydrate metabolism in experimental protein malnutrition

1980 ◽  
Vol 3 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Romesh Khardori ◽  
J. S. Bajaj ◽  
M. G. Deo ◽  
D. D. Bansal
Keyword(s):  
Insulin Secretion ◽  
Carbohydrate Metabolism ◽  
Protein Malnutrition

scholarly journals Maternal Protein Malnutrition Does Not Impair Insulin Secretion from Pancreatic Islets of Offspring after Transplantation into Diabetic Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e30685 ◽  
Author(s):  
Renato Chaves Souto Branco ◽  
Júlio Cezar de Oliveira ◽  
Sabrina Grassiolli ◽  
Rosiane Aparecida Miranda ◽  
Luiz Felipe Barella ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Diabetic Rats ◽  
Protein Malnutrition

Protein malnutrition after weaning disrupts peripheral clock and daily insulin secretion in mice

2017 ◽  
Vol 50 ◽  
pp. 54-65 ◽  
Author(s):  
Patricia Cristine Borck ◽  
Thiago Martins Batista ◽  
Jean Franciesco Vettorazzi ◽  
Rafael Ludemann Camargo ◽  
Antonio Carlos Boschero ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Malnutrition ◽  
Peripheral Clock ◽  
Daily Insulin

scholarly journals Estimation of insulin secretion, glucose uptake by tissues, and liver handling of glucose using a mathematical model of glucose-insulin homeostasis in lean and obese mice

Heliyon ◽  
2017 ◽  
Vol 3 (6) ◽  
pp. e00310 ◽  
Author(s):  
Michael Brenner ◽  
Sakineh Esmaeili Mohsen Abadi ◽  
Ramin Balouchzadeh ◽  
H. Felix Lee ◽  
Hoo Sang Ko ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Insulin Secretion ◽  
Glucose Uptake ◽  
Obese Mice ◽  
Insulin Homeostasis

scholarly journals SOX6 Attenuates Glucose-stimulated Insulin Secretion by Repressing PDX1 Transcriptional Actvity and Is Down-regulated in Hyperinsulinemic Obese Mice

2005 ◽  
Vol 280 (45) ◽  
pp. 37669-37680 ◽  
Author(s):  
Haruhisa Iguchi ◽  
Yukio Ikeda ◽  
Masashi Okamura ◽  
Toshiya Tanaka ◽  
Yasuyo Urashima ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Obese Mice ◽  
Glucose Stimulated Insulin Secretion

The influence of K+-induced membrane depolarization on insulin secretion in islets of lean and obese (ob/ob) mice

1990 ◽  
Vol 68 (1) ◽  
pp. 243-248 ◽  
Author(s):  
Linda A. Fournier ◽  
H. M. C. Heick ◽  
Nicole Bégin-Heick
Keyword(s):  
Insulin Secretion ◽  
Membrane Potential ◽  
Glucose Metabolism ◽  
Pertussis Toxin ◽  
Similar Response ◽  
Obese Mice ◽  
Induced Membrane ◽  
Voltage Dependent ◽  
Insulin Secretory Response ◽  
Altered Sensitivity

The present study was undertaken to determine whether factors that affect K+ permeability produce differences in insulin secretion in the islets of obese versus lean mice. At basal glucose (3 mM), the obese islets secreted more insulin for a given increment in depolarizing K+ concentration and responded to a wider range of K+ concentrations (5–45 mM) than the lean islets (5–25 mM). In contrast, the membrane potential changes induced by increments in pK+ were not significantly different in the two types of islets. The islets of lean and obese mice treated with pertussis toxin showed a qualitatively similar response to glucose and to epinephrine, but only the control and pertussis toxin treated obese islets responded to K+ depolarization when deprived of calcium. Abnormal responses to quinine and apamin were identified in the islets of obese mice. These findings show that the abnormal insulin secretory response of the obese islet is due, at least in part, to a defect independent of glucose metabolism. This is best explained by an altered sensitivity of voltage-dependent events, most likely the result of differential effects of an intracellular element acting on ATP-sensitive and Ca2+-activated K+ channels, both of which are implicated in membrane repolarization.Key words: pertussis toxin, voltage-activated Ca2+ channels, ATP-sensitive K+ channels, membrane potential.

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