Abnormal Insulin Secretory Response to Food after Acute Hypoglycaemia in Man: Evidence for β-Cell Glucopenia

1980 ◽  
Vol 59 (3) ◽  
pp. 16P-16P
Author(s):  
R. J. M. Corrall ◽  
B. M. Frier ◽  
J. P. Ashby ◽  
T. E. Adrian ◽  
S. R. Bloom
Keyword(s):  
Secretory Response ◽  
Β Cell ◽  
Insulin Secretory Response

THE EFFECT OF FASTING AND SELECTIVE RE-FEEDING ON INSULIN RELEASE IN THE RAT

1973 ◽  
Vol 72 (1) ◽  
pp. 46-53 ◽  
Author(s):  
D. S. Turner ◽  
D. A. B. Young
Keyword(s):  
Insulin Release ◽  
Acute Effect ◽  
Secretory Response ◽  
Release Mechanism ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Intravenous Glucose ◽  
Glucose Ingestion ◽  
Glucose Test ◽  
Insulin Secretory Response

ABSTRACT The insulin secretory response in the rat to intravenous glucose was found to be greatly impaired by fasting for three days, whereas that to orally administered glucose was not significantly affected. Rats fasted for two days were given either protein or starch pellets for six hours, and then fasted for a further eighteen hours before the intravenous glucose test. The protein pre-feeding failed to affect significantly the subsequent insulin secretory response to intravenous glucose, whereas starch prefeeding greatly enhanced it. It is suggested that intestinal hormones released by glucose ingestion may exert not only an acute effect on insulin release, but also a 'priming' effect on the insulin release mechanism of the β cell, which enables it to respond to the subsequent stimulus of glucose alone.

scholarly journals Inhibition of calpain blocks pancreatic β-cell spreading and insulin secretion

2005 ◽  
Vol 289 (2) ◽  
pp. E313-E321 ◽  
Author(s):  
Géraldine Parnaud ◽  
Eva Hammar ◽  
Dominique G. Rouiller ◽  
Domenico Bosco
Keyword(s):  
Insulin Secretion ◽  
Cell Attachment ◽  
Cell Spreading ◽  
Cysteine Proteases ◽  
Secretory Response ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Insulin Secretory Response ◽  
Calpain Inhibitors

In addition to promoting insulin secretion, an increase in cytosolic Ca2+ triggered by glucose has been shown to be crucial for spreading of β-cells attached on extracellular matrix (804G matrix). Calpains are Ca2+-dependent cysteine proteases involved in an extended spectrum of cellular responses, including cytoskeletal rearrangements and vesicular trafficking. The present work aimed to assess whether calpain is also implicated in the process of Ca2+-induced insulin secretion and spreading of rat pancreatic β-cells. The results indicate calpain dependency of β-cell spreading on 804G matrix. Indeed, treatment with three distinct calpain inhibitors (N-Ac-Leu-Leu-norleucinal, calpeptin, and ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butyl-carbamoyl]-2-ox-iranecarboxylate) inhibited cell spreading induced by glucose and KCl, whereas cell attachment was not significantly modified. Calpain inhibitors also suppressed glucose- and KCl-stimulated insulin secretion without affecting insulin synthesis. Washing the inhibitor out of the cell culture restored spreading on 804G matrix and insulin secretory response after 24 h. In addition, incubation with calpeptin did not affect insulin secretory response to mastoparan that acts on exocytosis downstream of intracellular calcium [Ca2+]i. Finally, calpeptin was shown to affect the [Ca2+]i response to glucose but not to KCl. In summary, the results show that inhibition of calpain blocks spreading and insulin secretion of primary pancreatic β-cells. It is therefore suggested that calpain could be a mediator of Ca2+-induced-insulin secretion and β-cell spreading.

scholarly journals Linearity of β-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series

2016 ◽  
Vol 310 (11) ◽  
pp. E865-E873 ◽  
Author(s):  
Sudha S. Shankar ◽  
R. Ravi Shankar ◽  
Lori A. Mixson ◽  
Deborah L. Miller ◽  
Christopher Chung ◽  
...  
Keyword(s):  
Cell Function ◽  
Secretory Response ◽  
Glucose Infusion ◽  
Response Patterns ◽  
Β Cell ◽  
Clinical Trial Registration ◽  
Hyperglycemic Clamp ◽  
Insulin Secretagogues ◽  
Insulin Secretory Response

The graded glucose infusion (GGI) examines insulin secretory response patterns to continuously escalating glycemia. The current study series sought to more fully appraise its performance characteristics. Key questions addressed were comparison of the GGI to the hyperglycemic clamp (HGC), comparison of insulin secretory response patterns across three volunteer populations known to differ in β-cell function (healthy nonobese, obese nondiabetic, and type 2 diabetic), and characterization of effects of known insulin secretagogues in the context of a GGI. Insulin secretory response was measured as changes in insulin, C-peptide, insulin secretion rates (ISR), and ratio of ISR to prevailing glucose (ISR/G). The GGI correlated well with the HGC ( r = 0.72 for ISR/G, P < 0.01). The insulin secretory response in type 2 diabetes (T2DM) was significantly blunted ( P < 0.001), whereas it was significantly increased in obese nondiabetics compared with healthy nonobese ( P < 0.001). Finally, robust ( P < 0.001 over placebo) pharmacological effects were observed in T2DM and healthy nonobese volunteers. Collectively, the findings of this investigational series bolster confidence that the GGI has solid attributes for assessing insulin secretory response to glucose across populations and pharmacology. Notably, the coupling of insulin secretory response to glycemic changes was distinctly and uniformly linear across populations and in the context of insulin secretagogues. (Clinical Trial Registration Nos. NCT00782418, NCT01055340, NCT01373450)

scholarly journals β-Cell Insulin Secretory Response to Oral Hypoglycemic Agents Is Blunted in Humansin Vivoduring Moderate Hypoglycemia

2004 ◽  
Vol 89 (9) ◽  
pp. 4553-4557 ◽  
Author(s):  
Waleed Aldhahi ◽  
Jen Armstrong ◽  
Clara Bouche ◽  
Richard D. Carr ◽  
Alan Moses ◽  
...  
Keyword(s):  
Secretory Response ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Β Cell ◽  
Insulin Secretory Response

scholarly journals Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC)

2021 ◽  
Author(s):  
Mina Hwang ◽  
Hyo‐Sup Kim ◽  
Sang‐Man Jin ◽  
Kyoo‐Yeon Hur ◽  
Jae‐Hyeon Kim ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Secretory Response ◽  
Insulin Secretory Response

scholarly journals Susceptibility to oxidative stress, insulin resistance, and insulin secretory response in the development of diabetes from obesity

2007 ◽  
Vol 64 (6) ◽  
pp. 391-397 ◽  
Author(s):  
Radivoj Kocic ◽  
Dusica Pavlovic ◽  
Gordana Kocic ◽  
Milica Pesic
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Lipid Peroxidation ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Critical Role ◽  
Secretory Response ◽  
Diabetic Patients ◽  
Apparent Difference ◽  
Insulin Secretory Response

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

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