Responsiveness and Memory of the Pancreatic B-Cells to the Insulin Secretagogues D-Glucose and L-Arginine in Prediabetic and Diabetic Rabbits

Fichaux, Françoise; Bonnafous, R.

doi:10.1097/00006676-199209000-00012

Cited by 7 publications

(3 citation statements)

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“…TDP occurs only in certain species such as human (7)(8)(9)(10), rat (2-6), rabbit (15), and spiny mouse (11). It is widely believed that TDP is absent in mice.…”

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confidence: 99%

Mechanisms of Time-Dependent Potentiation of Insulin Release

et al. 2006

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Time-dependent potentiation (TDP) of insulin release is normally absent in mice. However, we recently demonstrated that TDP occurs in mouse islets under conditions of forced decrease of intracellular pH (pH i ) associated with elevated NADPH؉H ؉ (NADPH) levels. Hence, TDP in mouse islets may be kept suppressed by neuronal nitric oxide (NO) synthase (nNOS), an NADPH-utilizing enzyme with alkaline pH optimum. To determine the role of nNOS in the suppression of TDP in mouse islets, glucose-induced TDP was monitored in mouse islets in which nNOS activity had been genetically removed or chemically inhibited and compared with the TDP response in wild-type mouse islets with and without forced intracellular acidification. Genetic deletion of nNOS was provided by an nNOS knockout (NOS-KO) mouse model, B6 -129S4-Nos1tm1Plh /J. To explore how nNOS inhibits TDP, we compared pH i and NADPH levels in wild-type and NOS-KO islets and monitored TDP with various components of the nNOS reaction added. Glucose normally does not produce TDP in wildtype mouse islets except under forced intracellular acidification. Remarkably, glucose produced strong TDP in NOS-KO islets and in wild-type islets treated with nNOS inhibitors. TDP in NOS-KO islets was not inhibited by the addition of NO, and NOS-KO islets exhibited a lower pH i than wild-type islets. The addition of arginine to wild-type islets also enabled glucose to induce TDP. Our results show that nNOS activity contributes to the absence of TDP in mouse islets putatively through depletion of intracellular arginine.

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“…TDP occurs only in certain species such as human (7)(8)(9)(10), rat (2-6), rabbit (15), and spiny mouse (11). It is widely believed that TDP is absent in mice.…”

mentioning

confidence: 99%

Mechanisms of Time-Dependent Potentiation of Insulin Release

et al. 2006

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“…TDP has been observed in in vitro preparations of islets and pancreases from different species, including rat (17-19, 21, 55-57), rabbit (15), and spiny mouse (37), as well as in in vivo studies in humans (4 -7, 39). TDP occurs simultaneously with time-dependent inhibition (TDI) but lasts longer than TDI (5,11,38,39).…”

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confidence: 99%

Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets

Gunawardana¹,

Liu²,

MacDonald³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Nutrients that induce biphasic insulin release, such as glucose and leucine, provide acetyl-CoA and anaplerotic input in the beta-cell. The first phase of release requires increased ATP production leading to increased intracellular Ca(2+) concentration ([Ca(2+)](i)). The second phase requires increased [Ca(2+)](i) and anaplerosis. There is strong evidence to indicate that the second phase is due to augmentation of Ca(2+)-stimulated release via the K(ATP) channel-independent pathway. To test whether the phenomenon of time-dependent potentiation (TDP) has similar properties to the ATP-sensitive K(+) channel-independent pathway, we monitored the ability of different agents that provide acetyl-CoA and anaplerotic input or both of these inputs to induce TDP. The results show that anaplerotic input is sufficient to induce TDP. Interestingly, among the agents tested, the nonsecretagogue glutamine, the nonhydrolyzable analog of leucine aminobicyclo[2.2.1]heptane-2-carboxylic acid, and succinic acid methyl ester all induced TDP, and all significantly increased alpha-ketoglutarate levels in the islets. In conclusion, anaplerosis that enhances the supply and utilization of alpha-ketoglutarate in the tricarboxylic acid cycle appears to play an essential role in the generation of TDP.

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“…This ªmemoryº seems to be unrelated to the rate of insulin synthesis. Thus, glucose infusion intensifies a subsequent argininestimulated insulin release, whereas arginine inhibits the insulin response to a succeeding glucose stimulus [23]. If regular pulsatile insulin release synchronizes the insulin pools or primes the beta-cell memory for immediate response, one might expect that an irregular release pattern would be disadvantageous in terms of the acute insulin response to glucose and GLP-1.…”

Section: Discussionmentioning

confidence: 99%

Acute Insulin Responses to Intravenous Glucose and GLP-1 are Independent of Preceding High-frequency Insulin Pulse-defects Induced by Glucose Entrainment in Healthy Humans

Juhl¹,

Sturis²,

Hollingdal³

et al. 2005

Horm Metab Res

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The objective of this study was to test the hypothesis that high-frequency oscillations in insulin release is a part of the mechanistic basis of a prompt and adequate insulin response to iv-glucose and GLP-1 exposure. In ten healthy subjects, five different insulin release patterns were induced for 360 min using computer-based glucose infusion (glucose delivered in a constant, a regular pulsatile, an irregular pulse frequency, an irregular pulse amplitude or a regular but very fast-pulsatile manner) in healthy subjects. The amount of glucose infused was identical in all five protocols (24 mg/kg/h). After 360 min, insulin secretion was assessed by means of a first-phase insulin secretion test (25 g glucose) and injection of GLP-1 (9 microg). By frequent blood sampling and analysis of insulin concentration, glucose-induced entrainment was evident in all protocols except in the constant infusion and the very fast-pulse protocol. The first-phase insulin release to glucose and GLP-1-induced insulin release were, however, comparable in the protocols. We therefore conclude from this short-term experimental setting in healthy subjects that beta-cell response to either iv-glucose or GLP-1 is independent of the preceding regularity of oscillations in insulin release.

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Responsiveness and Memory of the Pancreatic B-Cells to the Insulin Secretagogues D-Glucose and L-Arginine in Prediabetic and Diabetic Rabbits

Cited by 7 publications

References 0 publications

Mechanisms of Time-Dependent Potentiation of Insulin Release

Mechanisms of Time-Dependent Potentiation of Insulin Release

Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets

Acute Insulin Responses to Intravenous Glucose and GLP-1 are Independent of Preceding High-frequency Insulin Pulse-defects Induced by Glucose Entrainment in Healthy Humans

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