Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities

Grill, V.; Björklund, Anneli

doi:10.1007/pl00000705

Cited by 32 publications

(30 citation statements)

References 104 publications

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“…A diminished insulin response to acute glucose stimulation (glucose desensitization) has been reported to characterize islets subjected to chronic hyperglycemia in vitro (34 -36) and in vivo (16,(37)(38)(39)(40)(41). In contrast, an increased glucose sensitivity characterized islets from 90% pancreatectomized rats (42), dexamethasone-treated (43) and 48-h glucose-infused rats (44), and normal rat islets cultured for several days in the presence of high glucose concentrations (45)(46)(47). However, the occurrence of maximal stimulation of insulin secretion at low physiological glucose concentration, as observed in DP-HE islets and in other models of chronic hyperglycemia (48), could be easily misinterpreted as a lack of glucose-induced insulin secretion if only tested between 4 and 10 -20 mmol/l glucose (42,46).…”

Section: Discussionmentioning

confidence: 99%

Increased Glucose Sensitivity of Stimulus-Secretion Coupling in Islets FromPsammomys obesusAfter Diet Induction of Diabetes

Pertusa¹,

Нешер

Kaiser

et al. 2002

Diabetes

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When fed a high-energy (HE) diet, diabetes-prone (DP) Psammomys obesus develop type 2 diabetes with altered glucose-stimulated insulin secretion (GSIS).␤-Cell stimulus-secretion coupling was investigated in islets isolated from DP P. obesus fed a low-energy (LE) diet (DP-LE) and after 5 days on a HE diet (DP-HE). DP-LE islets cultured overnight in 5 mmol/l glucose displayed glucose dose-dependent increases in NAD(P)H, mitochondrial membrane potential, ATP/ (ATP ؉ ADP) ratio, cytosolic calcium concentration ([Ca 2؉ ] c ), and insulin secretion. In comparison, DP-HE islets cultured overnight in 10 mmol/l glucose were 80% degranulated and displayed an increased sensitivity to glucose at the level of glucose metabolism, [Ca 2؉ ] c , and insulin secretion. These changes in DP-HE islets were only marginally reversed after culture in 5 mmol/l glucose and were not reproduced in DP-LE islets cultured overnight in 10 mmol/l glucose, except for the 75% degranulation. Diabetes-resistant P. obesus remain normoglycemic on HE diet. Their ␤-cell stimulus-secretion coupling was similar to that of DP-LE islets, irrespective of the type of diet. Thus, islets from diabetic P. obesus display an increased sensitivity to glucose at the level of glucose metabolism and a profound ␤-cell degranulation, both of which may affect their in vivo GSIS. Diabetes 51:2552-2560, 2002 S timulation of insulin secretion by glucose requires oxidative metabolism of the sugar in ␤-cells, with acceleration of ATP production and increase of the ATP/ADP ratio (1-4). The subsequent closure of ATP-sensitive K ϩ channels in the plasma membrane is followed by depolarization, opening of voltage-dependent Ca 2ϩ channels, and Ca 2ϩ influx. This leads to a rise with oscillations of the cytosolic calcium concentration ([Ca 2ϩ ] c ), which triggers exocytosis of insulin-containing granules (5-7). Glucose metabolism also amplifies the efficacy of [Ca 2ϩ ] c on exocytosis, but the nature of the coupling factor(s) remains elusive (8).Type 2 diabetes is characterized by the association of insulin resistance and inappropriate insulin secretion by pancreatic ␤-cells (9 -12). The gerbil Psammomys obesus is an attractive model of diet-induced type 2 diabetes because a diabetes-resistant (DR) subgroup has been separated from the diabetes-prone (DP) animals by assorted breeding (9,13). When fed a low-energy (LE) diet, DP P. obesus remain normoglycemic despite their marked insulin resistance. Within a few days on a high-energy (HE) diet, DP P. obesus develop hyperglycemia associated with hyperinsulinemia, rapidly followed by a progressive decline in ␤-cell function leading to absolute insulin deficiency (14,15). In contrast, DR P. obesus are less hyperinsulinemic and remain normoglycemic on HE diet (16). Previous studies have shown that after 5 days on HE diet, glucose-stimulated insulin secretion (GSIS) is markedly altered in islets from DP but not DR P. obesus, possibly as a result of decreased insulin content, lower oxidative capacity, and altered protein kinase C ac...

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Section: Discussionmentioning

confidence: 99%

Increased Glucose Sensitivity of Stimulus-Secretion Coupling in Islets FromPsammomys obesusAfter Diet Induction of Diabetes

Pertusa¹,

Нешер

Kaiser

et al. 2002

Diabetes

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“…These areas were explored first because of their proposed roles as "feeding" and "satiety" centers respectively, making it logical that they might monitor peripheral glucose levels as a means of controlling ingestion (Grill and Bjorklund 2000). Since postprandial hyperglycemia has been recognized as an important risk factor for cardiovascular diseases, even among general healthy population (Coutinho et al 1999), it becomes necessary to manage glucose homeostasis by diet and its constituents.…”

Section: Plasma Hormonesmentioning

confidence: 99%

Effectual comparison of quinoa and amaranth supplemented diets in controlling appetite; a biochemical study in rats

Mithila

Khanum

2015

J Food Sci Technol

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The objective of this study was to assess the efficacy of two current cynosure protein substitutes; quinoa and amaranth in controlling short term food intake and satiety in rats. Experimental rats were allotted to three groups (n=8 per group) and fed with diets containing casein, quinoa and amaranth as major protein sources, with casein diet kept as control. At the end of the experiment it was observed that the rats ingesting quinoa and amaranth supplemented diets exhibited lesser food intake (p<0.01) and lesser body weight gain significantly in amaranth (p<0.05) as compared to control. They seemed to bring down plasma ghrelin levels while meliorating plasma leptin and cholecystokinin (CCK) levels postprandially (p < 0.01). Although both quinoa diet and amaranth diet were effective in improving blood glucose response and maintaining plasma free fatty acids (FFA) and general lipid profiles subsequently after the meal, amaranth diet showed significant effects when compared to control and amaranth diets. There was 15 % improvement in blood glucose profile in the amaranth group with respect to the control at 90 min, where as there was only 3.4 % improvement in the quinoa group. These findings provide a scientific rationale to consider incorporation of these modest cereals in a diet meant to fight against growing obesity and poverty.

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“…Dysregulation of any of these aspects of the nutrient response and/or alterations in ␤-cell differentiation and survival are potentially implicated in the onset of type 2 diabetes. This disease is associated with peripheral insulin resistance but only develops in conjunction with a failure of ␤-cell compensation, which otherwise counteracts the insulin resistance (2)(3)(4)(5). Type 2 diabetic patients display reductions in ␤-cell mass as compared with insulin-resistant nondiabetic individuals, as well as a number of clearly defined secretory abnormalities.…”

mentioning

confidence: 99%

“…Although ongoing hyperglycemia is undoubtedly a major contributor to ␤-cell decompensation, it is apparent that chronic elevations in circulating fatty acids (FAs) also accompany the progression to type 2 diabetes (3)(4)(5). Since FAs themselves stimulate insulin secretion, a key role in secretory compensation has been ascribed to their elevation (4,6).…”

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confidence: 99%

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

Busch

Cordery²,

Denyer³

et al. 2002

Diabetes

175

139

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Chronic lipid exposure is implicated in ␤-cell dysfunction in type 2 diabetes. We therefore used oligonucleotide arrays to define global alterations in gene expression in MIN6 cells after 48-h pretreatment with oleate or palmitate. Altogether, 126 genes were altered >1.9-fold by palmitate, 62 by oleate, and 46 by both lipids. Importantly, nine of the palmitate-regulated genes are known to be correspondingly changed in models of type 2 diabetes. A tendency toward ␤-cell de-differentiation was also apparent with palmitate: pyruvate carboxylase and mitochondrial glycerol 3-phosphate dehydrogenase were downregulated, whereas lactate dehydrogenase and fructose 1,6-bisphosphatases were induced. Increases in the latter (also seen with oleate), along with glucosamine-phosphate N-acetyl transferase, imply upregulation of the hexosamine biosynthesis pathway in palmitate-treated cells. However, palmitate also increased expression of calcyclin and 25-kDa synaptosomal-associated protein (SNAP25), which control distal secretory processes. Consistent with these findings, secretory responses to noncarbohydrate stimuli, especially palmitate itself, were upregulated in palmitate-treated cells (much less so with oleate). Indeed, glucose-stimulated secretion was slightly sensitized by chronic palmitate exposure but inhibited by oleate treatment, whereas both lipids enhanced basal secretion. Oleate and palmitate also induced expression of chemokines (MCP-1 and GRO1 oncogene) and genes of the acute phase response (

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Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities

Cited by 32 publications

References 104 publications

Increased Glucose Sensitivity of Stimulus-Secretion Coupling in Islets FromPsammomys obesusAfter Diet Induction of Diabetes

Increased Glucose Sensitivity of Stimulus-Secretion Coupling in Islets FromPsammomys obesusAfter Diet Induction of Diabetes

Effectual comparison of quinoa and amaranth supplemented diets in controlling appetite; a biochemical study in rats

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

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