Adenosine Triphosphate Levels of Mammalian Pancreatic B Cells after Stimulation with Glucose and Hypoglycemic Sulfonylureas

Hellman, Bo; Idahl, Lars-Åke; Danielsson, Åke

doi:10.2337/diab.18.8.509

Cited by 98 publications

(49 citation statements)

References 27 publications

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“…Furthermore, islets cultured with high glucose contain ten times more glycogen than islets from low-glucose media [23]. The high glycogen content might cause a substantial production of glucose intermediates in the presence of sulfonylureas, which are known to exert a marked glycogenolytic effect on the B-cells [24]. This effect may consequently explain the larger insulin response to glibenclamide in the high-glucose cultured islets.…”

Section: Discussionmentioning

confidence: 76%

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

et al. 1975

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Summary. Microdissected pancreatic islets from non-inbred ob/ ob-mice were cultured for 6 or 7 days in serum-free tissue culture medium 199. The insulin content of the islets decreased 60% during culture in 17 mM or 28 mM glucose and about 70% in the presence of 3.3 mM or 5.6 mM glucose. At the end of a culture period in high glucose, the sum of the insulin in the islet plus that in the culture medium was almost twice as high as the insulin content of fresh islets, indicating an active insulin biosynthesis. The maximal insulin response to glucose after culture in 17 mM or 28 mM glucose was about 40% of that in fresh islets; after culture in 3.3 mM glucose it was 10%. Half-maximal stimulation was observed at a glucose concentration of 5 mM for islets cultured with high glucose as compared to 9 mM for fresh islets. Like glucose, glibenclamide was a more effective insulin stimulator after culture with a high glucose concentration than with a low one. However, leucine-induced insulin release was not affected by the glucose concentration in the preceding culture medium. Whereas potentiation of glucose-stimulated release by arginine or dibutyryl-cAMP was independent of glucose concentration during the culture, theophylline released three times more insulin when the islets had been cultured with high glucose.

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Section: Discussionmentioning

confidence: 76%

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

et al. 1975

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“…In mouse islets incubated in the absence of exogenous fuels, tolbutamide (about 400 μmol/l free concentration) slightly stimulated oxygen consumption [26,42]. Decrease in ATP content induced by high sulfonylurea concentrations was observed in mouse and rat islets incubated in the absence of exogenous fuels or in the presence of low glucose concentrations [43][44][45][46]. Mild mitochondrial depolarisation is the likely reason why glipizide caused glucose and α-ketoisocaproate to induce only a small increase in the islet ATP/ADP ratio [12].…”

Section: Discussionmentioning

confidence: 85%

Fuel-induced amplification of insulin secretion in mouse pancreatic islets exposed to a high sulfonylurea concentration: role of the NADPH/NADP+ ratio

Panten

Rustenbeck

2007

Diabetologia

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Aims/hypothesis The aim of this study was to examine whether the cytosolic NADPH/NADP + ratio of beta cells serves as an amplifying signal in fuel-induced insulin secretion and whether such a function is mediated by cytosolic α-ketoglutarate. Methods Pancreatic islets and islet cells were isolated from albino mice by collagenase digestion. Insulin secretion of incubated or perifused islets was measured by ELISA. The NADPH and NADP + content of incubated islets was determined by enzymatic cycling. The cytosolic Ca 2+ concentration ([Ca 2+ ] c ) in islets was measured by microfluorimetry and the activity of ATP-sensitive K + channels in islet cells by patch-clamping. Results Both 30 mmol/l glucose and 10 mmol/l α-ketoisocaproate stimulated insulin secretion and elevated the NADPH/NADP + ratio of islets preincubated in the absence of fuel. The increase in the NADPH/NADP + ratio was abolished in the presence of 2.7 μmol/l glipizide (closing all ATP-sensitive K + channels). However, α-ketoisocaproate, but not glucose, still stimulated insulin secretion. That glipizide did not inhibit α-ketoisocaproate-induced insulin secretion was not the result of elevated [Ca 2+ ] c , as glucose caused a more marked [Ca 2+ ] c increase. Insulin release triggered by glipizide alone was moderately amplified by dimethyl α-ketoglutarate (which is cleaved to produce cytosolic α-ketoglutarate), but there was no indication of a signal function of cytosolic α-ketoglutarate. Conclusions/interpretationThe results strongly suggest that the NADPH/NADP + ratio in the beta cell cytosol does not serve as an amplifying signal in fuel-induced insulin release. The study supports the view that amplification results from the intramitochondrial production of citrate by citrate synthase and from the associated export of citrate into the cytosol.

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“…Thus, a direct action of the drugs on the beta cells emerges as the most likely cause of these observations. In support of this conclusion, the foliowing evidence may be cited: carbutamide and glibenclamide lower the ATP [46] and the glucose-6-phosphate content of isolated islets [46,47], even as glibenclamide and tolbutamide increase their oxygen consumption and laetate production [33,48]. Thus, although there is some exddenee to the contrary [37,49], the sulfonylureas may uncouple oxidative phosphorylation in the islets, as they appear to do in liver, diaphragm and adipose tissue [50,51].…”

Section: Discussionmentioning

confidence: 87%

An inhibitory effect of tolbutamide and glibenclamide (glyburide) on the pancreatic islets of normal animals

Dunbar

Foà

1974

Diabetologia

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Summary. Tolbutamide and glibenelamide (glyburide) were administered to normal hamsters, mice or rats in daily doses proportional to their body weight and equivalent to those used in human therapy. The animals were sacrificed after 6 to 8 weeks of treatment. Pieces of pancreas or isolated pancreatic islets were incubated or perifused in a medium containing glucose or tolbutamide, with or without leueine-114C or glucose-U-14C. The results indicate that the B cells of sulfonylurea treated animals synthesized and released less insulin and oxidized less glucose than those of insulin or saline treated controls. Accordingly, at least in the glibenelamide treated animals, the tolerance for glucose and the insulinogenie response to a glucose load in vivo were suppressed. Although insular function tended to return.to normal after treatment was discontinued, the results reported in this paper do not support the generally aeeepted view that the lasting therapeutic effectiveness of the sulfonylureas is due to a beta-cytotrophie action.

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Adenosine Triphosphate Levels of Mammalian Pancreatic B Cells after Stimulation with Glucose and Hypoglycemic Sulfonylureas

Cited by 98 publications

References 27 publications

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

Function of microdissected pancreatic islets cultured in a chemically defined medium. I. Insulin content and release

Fuel-induced amplification of insulin secretion in mouse pancreatic islets exposed to a high sulfonylurea concentration: role of the NADPH/NADP+ ratio

An inhibitory effect of tolbutamide and glibenclamide (glyburide) on the pancreatic islets of normal animals

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