Dynamics of Insulin Secretion by the Perfused Rat Pancreas

Curry, Donald L.; Bennett, Leslie L.; Grodsky, Gerold M.

doi:10.1210/endo-83-3-572

Cited by 575 publications

(370 citation statements)

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“…The remaining vesicles within the cytosol further from the membrane comprise the RP of insulin vesicles (Bratanova-Tochkova et al, 2002). Insulin secretion from the β cell in response to a square wave stimulatory increase in glucose concentration from the resting state occurs in two phases both in vitro and in vivo (Cerasi and Luft, 1963;Curry et al, 1968). The first phase is rapid, lasts for about 10-15 min, and reaches a peak within 10 min in the mouse .…”

Section: Glp-1 Effects On the Readily Releasable Pool (Rrp)mentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

551

445

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Section: Glp-1 Effects On the Readily Releasable Pool (Rrp)mentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

551

445

View full text Add to dashboard Cite

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“…The release of insulin is biphasic; a first rapid phase of secretion is followed by a second phase with slower release (Curry et al, 1968). Prior to release insulin is contained in secretory granules.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Pedersen

Cortese

Eliasson

2011

Progress in Biophysics and Molecular Biology

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“…The insulin response to a hyperglycaemic stimulation is biphasic [3]. Insulin concentrations in the plasma increase rapidly to a peak at 2 to 4 min, decrease to a nadir at 10 to 15 min and then gradually increase over 120 to 180 min.…”

Section: Introductionmentioning

confidence: 99%

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

et al. 2007

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Aims/hypothesis We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. Methods Non-diabetic offspring (n=874; mean age 40± 10.4 years; BMI 26.6±4.9 kg/m 2 ) of type 2 diabetic patients from five different European Centres (Denmark, Finland, Germany, Italy and Sweden) were examined with regard to insulin sensitivity (euglycaemic clamps), insulin release (IVGTT) and glucose tolerance (OGTT). The levels of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) were measured during the OGTT in 278 individuals. Results Normal glucose tolerance was found in 634 participants, while 110 had isolated IFG, 86 had isolated IGT and 44 had both IFG and IGT, i.e. about 28% had a form of reduced glucose tolerance. Participants with isolated IFG had lower glucose-corrected first-phase (0-10 min) and higher second-phase insulin release (10-60 min) during the IVGTT, while insulin sensitivity was reduced in all groups with abnormal glucose tolerance. Similarly, GLP-1 but not GIP levels were reduced in individuals with abnormal glucose tolerance. Conclusions/interpretation The primary mechanism leading to hyperglycaemia in participants with isolated IFG is likely to be impaired basal and first-phase insulin secretion, whereas in isolated IGT the primary mechanism leading to postglucose load hyperglycaemia is insulin resistance. Reduced GLP-1 levels were seen in all groups with abnormal glucose tolerance and were unrelated to the insulin release pattern during an IVGTT.

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Dynamics of Insulin Secretion by the Perfused Rat Pancreas

Cited by 575 publications

References 0 publications

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

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