In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

Liang, Yin; Bonner-Weir, Susan; Wu, Yuelong; Berdanier, Carolyn D.; Berner, Donna K; Efrat, Shimon; Matschinsky, Franz M.

doi:10.1172/jci117256

Cited by 37 publications

(22 citation statements)

References 48 publications

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“…These features are diet responsive [1,3,4,23]. In addition, we have already reported on the deterioration in insulin release by isolated islets as these rats age [6] as well as the influence of diet on this age progression [1,24,25]. The expression of the diabetes phenotype in humans likewise is subject to dietary influence.…”

Section: Discussionmentioning

confidence: 99%

“…This rat strain shows a reduction in ATP synthesis efficiency, mitochondrial coupling and b-cell ATP content. A decline in glucose stimulated insulin release also occurs with age [6]. Glucose stimulated insulin release falls from 89.5 ± 10.2 pmol/l to 46.3 ± 22.7 pmol/l at 30 s post glucose injection and from 97.6 ± 21.4 pmol/l to 74.6 ± 11.0 pmol/l at 60 s as the animals age from 50 to 300 days of age.…”

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confidence: 93%

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Inheritance of a mitochondrial DNA defect and impaired glucose tolerance in BHE/Cdb rats

et al. 1999

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The BHE/Cdb rat strain is an inbred strain that develops impaired glucose tolerance at maturity. The diabetic state is preceded by defects in metabolism that progress with age. Environmental factors, such as diet, affect the time frame for the phenotypic expression of the genotype [1]. Feeding sugar rich and fat rich diets hastens the appearance of impaired glucose tolerance and its complications. The diabetic phenotype has been attributed to point mutations (bp 8204, 8289) in the mtDNA gene for F o ATPase subunit 6 [2] and Herrnstad, (personal communication) because these rats show impaired mitochondrial function, particularly in the control of oxidative phosphorylation [3±5]. No evidence of a point mutation in the tRNA LEU(UUR) has been found nor have we found evidence of muscle or nerve pathology. This rat strain shows a reduction in ATP synthesis efficiency, mitochondrial coupling and b-cell ATP content. A decline in glucose stimulated insulin release also occurs with age [6]. Glucose stimulated insulin release falls from 89.5 ± 10.2 pmol/l to 46.3 ± 22.7 pmol/l at 30 s post glucose injection and from 97.6 ± 21.4 pmol/l to 74.6 ± 11.0 pmol/l at 60 s as the animals age from 50 to 300 days of age. Corresponding values in Sprague Dawley rats (SD) at 300 days of age were 74.6 ± 38.2 pmol/l and 110.7 ± 12.2 pmol/l. The values from BHE/Cdb rats were roughly 30 % less than those of the SD rats. Islets isolated from these rats release 65 % less insulin than islets from control rats of the same age when stimulated by the addition of glucose to the incubation medium. There was, however, only a small difference in islet insulin content (0.021 ± 0.002 pmol/g, 0.020 ± 0.009 pmol/g dry tissue, SD vs BHE/Cdb) at 50 days of age.The F o ATPase subunit 6 (also called subunit a) mutation [2] could account for the age related decline in ATP synthesis efficiency and subsequent alterations in glucose metabolism. A maternal mode of in- Diabetologia (1999) Summary As they age, BHE/Cdb rats develop impaired glucose tolerance. We hypothesized that this intolerance is associated with a previously reported base substitution in the mitochondrial genome. A new screening test was devised to identify animals with the mutation. These animals were bred to animals without the mutation. The progeny were then tested for the presence of the mutation and their glucose tolerance at 100 and 300 days of age. Phenotype and genotype were found to be closely linked and we conclude that the mutation in the mitochondrial ATPase 6 gene explains the age related impaired glucose tolerance in BHE/Cdb rats. [Diabetologia (1999) heritance of the Type II (non-insulin-dependent) diabetes mellitus trait was suspected based on breeding records. If the impaired glucose tolerance was due to the mitochondrial defect, both the impaired glucose tolerance and the DNA mutation should follow a maternal inheritance pattern. To test this hypothesis a cross breeding study of glucose tolerance and mt ATPase sequence was conducted using, as parents, animals with or witho...

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Section: Discussionmentioning

confidence: 99%

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confidence: 93%

Inheritance of a mitochondrial DNA defect and impaired glucose tolerance in BHE/Cdb rats

et al. 1999

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“…Consequently, the efficiency of oxidative phosphorylation is compromised [3] and ATP production is reduced [4]. Previous studies established that aged male BHE/cdb rats had abnormal islet morphology, but relatively normal insulin content [5]. Glucose-stimulated insulin secretion (GSIS) was reduced, but could not be attributed to changes in glucokinase activity or islet glucose uptake [5].…”

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confidence: 99%

Mutated ATP synthase induces oxidative stress and impaired insulin secretion in β‐cells of female BHE/cdb rats

Saleh

Fatehi‐Hassanabad

Wang

et al. 2008

Diabetes Metabolism Res

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“…Two isoforms of the enzyme, the liver and islet isoforms, have been identified as consistent with molecular genetic information (2,3). Significant information has been collected during the last 30 years in careful measurements of catalytic activities (8,9), mRNA levels (10,11), and protein contents (10 -12) of GK and other phenomena related to expression regulation of the enzyme and has formed the basis of a viewpoint called here the "classic view of GK regulation" (13). According to this concept, insulin is the prime mover in GK induction in hepatocytes, and glucose is the critical factor for GK induction in pancreatic ␤-cells.…”

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confidence: 99%

Regulation of Pancreatic β-Cell Glucokinase

2002

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In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

Cited by 37 publications

References 48 publications

Inheritance of a mitochondrial DNA defect and impaired glucose tolerance in BHE/Cdb rats

Inheritance of a mitochondrial DNA defect and impaired glucose tolerance in BHE/Cdb rats

Mutated ATP synthase induces oxidative stress and impaired insulin secretion in β‐cells of female BHE/cdb rats

Regulation of Pancreatic β-Cell Glucokinase

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