Pancreatic islet glucose metabolism and regulation of insulin secretion

Meglasson, M. D.; Matschinsky, Franz M.

doi:10.1002/dmr.5610020301

Cited by 484 publications

(368 citation statements)

References 200 publications

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“…When considering our results, an important issue is the normal beta-cell sensor for glucose metabolism and insulin secretion is glucokinase, the high K m glucose phosphorylation enzyme [35,36]. Hexokinase is present in beta-cells in amounts comparable to glucokinase [37], but it normally has a minimal regulatory role over glucose metabolism because of insensitivity to physiological levels of glucose and endproduct inhibition by glucose 6-phosphate [38,39]. As such, a shift in the glucose set-point for insulin secretion would be predicted to reflect a variation in glucokinase activity.…”

Section: Discussionmentioning

confidence: 88%

Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

1997

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Section: Discussionmentioning

confidence: 88%

Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

1997

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“…While there is evidence to suggest that glucose exerts its effect through its own metabolism, resulting in the creation of signals that appear to work through modulation of ion channel activities and influx of extracellular Ca 2 + , the exact nature of the metabolic coupling factors remains unknown. For a summary of current thinking about these issues, a subject that is beyond the scope of this article, the reader is referred to recent reviews [2][3][4][5]. The magnitude of the insulin secretory response appears to be related to the rate of beta-cell glucose metabolism, and both parameters are sharply increased in response to modest increments in extracellular glucose concentrations within the physiological range of 4 to 8 mmol/l.…”

Section: : S 42-s 47]mentioning

confidence: 99%

Engineered cell lines for insulin replacement in diabetes: current status and future prospects

Newgard

Clark²,

BeltrandelRio

et al. 1997

Diabetologia

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The recently concluded diabetes control and complications trial (DCCT) [1] has emphatically underscored the potential for improvement in current treatment protocols for diabetes mellitus. 'Conventional' insulin therapy, involving 1-2 injections of the hormone per day and intermittent glucose monitoring is clearly not as effective at slowing the progression of the debilitating and costly secondary complications of the disease as 'tight control', in which insulin pumps or multiple injections are combined with frequent glucose monitoring to limit hyperglycaemic excursions. Unfortunately, improvement in glycaemic control through increased insulin dosing requires a new level of compliance and discipline, and places the patient at significantly enhanced risk for dangerous hypoglycaemic episodes. These concerns have produced a surprising reticence among both physicians and patients towards implementation of tight control therapy. This reaction has served to place a new emphasis on the design of better methods for insulin replacement in insulin-dependent diabetes mellitus (IDDM). A primary consideration in such work is to develop a 'closed loop' system in which the hormone is delivered in response to metabolic demand, thereby eliminating the need for self monitoring by the patient. Three basic approaches to achieving this end have been contemplated, and are being investigated with ever increasing vigour. The first involves development of mechanical devices consisting of a pump or other mechanism for insulin delivery linked to a detector system for blood glucose. The second involves transplantation of insulin-producing cells from human or large mammal donors into IDDM patients. This can be achieved by transplantation of the entire pancreas or isolated pancreatic islets. Because of the difficulty and cost associated with islet isolation and pancreas transplantation, a third approach has emerged, in which the tools of molecular biology are used to fashion insulin-secreting cell lines with fuelmediated insulin secretion responses resembling Diabetologia (1997) Summary The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas transplantation over the past three decades, the broad-scale applicability of these approaches remains uncertain due in part to the difficulty and expense associated with procurement of functional tissue. To address this concern, we and others have been using the tools of molecular biology to develop cell lines with regulated insulin secretion that might serve as a surrogate for primary islets or pancreas tissue in transplantation therapy. This article seeks to provide a brief summary of the current status of this growing field, with a particular emphasis on progress in producing cell lines with appropriate glucose-stimulated insulin secretion. [Diabetologia (1997) 40: S 42-S 47]

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“…However, the regulation of hepatic and fcell glucokinases differs in a way related to the functions of the two cell types. Whereas hepatic glucokinase modulates glucose uptake, fl-cell glucokinase may play the role of a glucose sensor (reviewed in [5]). By controlling the rate of the glycolytic flux in f, cells, glucokinase determines the ATP:ADP ratio, which is postulated to affect insulin secretion.…”

Section: Glucokinasementioning

confidence: 99%

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

Lemaigre¹,

Rousseau²

1994

Biochemical Journal

100

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Pancreatic islet glucose metabolism and regulation of insulin secretion

Cited by 484 publications

References 200 publications

Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

Beta-cell hypersensitivity to glucose following 24-h exposure of rat islets to fatty acids

Engineered cell lines for insulin replacement in diabetes: current status and future prospects

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

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