Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats

Östenson, Claes‐Göran; Abdel‐Halim, Samy M.; Rasschaert, Joanne; Malaisse‐Lagae, Francine; Meuris, Sylvain; Sener, Abdullah; Efendić, Suad; Malaisse, Willy

doi:10.1007/bf00401142

Cited by 98 publications

(58 citation statements)

References 24 publications

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“…These observations are in contrast to those in previous reports in which enzyme activity and the mGPDH protein level decreased to 30±40 % of those in control Wistar rats [11,16]. This may be due to differences in genetic or environmental conditions (e. g. colony, age, food, etc.).…”

Section: Discussioncontrasting

confidence: 96%

“…The impaired glucose-stimulated insulin secretion observed in GK rats has been suggested to be attributable, at least in part, to a concomitant decrease in mGPDH activity which leads to decreased glycerol phosphate shuttle activity [4,11]. Although the decrease in mGPDH activity was modest (79 % of control) in our GK rats, it is still possible that the decreased activity would explain, at least in part, the severely impaired insulin secretion, given that glycerol phosphate shuttle activity is one of the key steps in glucose metabolism in beta cells, and thus in glucosestimulated insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of this enzyme is especially high in the pancreatic islets of rodents [8,9] and humans [10], suggesting the importance of this enzyme in insulin secretory tissue. The activity of mGPDH has been shown to be decreased in the islets of GK rats [11], as well as in those of other rodent models of NIDDM, such as rats injected with streptozotocin in the neonatal period [12], db/db mice [13] and fa/fa rats [14], and in humans [15]. These lines of evidence suggest that decreased mGPDH activity and the resultant decrease in glycerol phosphate shuttle activity may be responsible, at least in part, for the impaired insulin secretion in both the animal models and human NIDDM.…”

Section: : 649±653]mentioning

confidence: 99%

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Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets

et al. 1998

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In the GK (Goto-Kakizaki) rat, a spontaneous diabetic rodent model produced by repeated selective breeding of the Wistar rat, the insulin secretory response to glucose is selectively impaired [1,2] as in human non-insulin-dependent diabetes mellitus (NIDDM) patients [3]. Because the defect is specific for glucose-stimulated insulin secretion, the metabolic glucose signal appears to be impaired [4,5]. Glucose must enter beta cells and be metabolized via glycolytic and mitochondrial oxidative pathways in order to stimulate insulin release. The resulting changes in the intracellular ATP/ADP ratio close the ATP dependent potassium channel (K-ATP), leading to membrane depolarization, Ca 2+ entry and insulin exocytosis. In GK rats, it was suggested that the step responsible for the metabolic dysfunction of beta cells is located within the glycolytic pathway before Diabetologia (1998) Summary Glucose-stimulated insulin secretion is impaired in GK (Goto-Kakizaki) rats, perhaps because of abnormalities in glucose metabolism in pancreatic islet beta cells. The glycerol phosphate shuttle plays a major role in glucose metabolism by reoxidizing cytosolic NADH generated by glycolysis. In the pancreatic islets of GK rats, the activity of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate shuttle, is decreased and this abnormality may be responsible, at least in part, for impaired glucose-stimulated insulin secretion. To investigate this possibility, we overexpressed mGPDH in islets isolated from GK rats via recombinant adenovirus-mediated gene transduction, and examined glucose-stimulated insulin secretion. In islets isolated from diabetic GK rats at 8 to 10 weeks of age, glucose-stimulated insulin secretion was severely impaired, and mGPDH activity was decreased to 79 % of that in non-diabetic Wistar rats. When mGPDH was overexpressed in islets from GK rats, enzyme activity and protein content increased 2-and 6-fold, respectively. Basal (3 mmol/l glucose) and glucose-stimulated (20 mmol/l) insulin secretion from the Adex1CAlacZ-infected GK rat islets were, respectively, 4.4 ± 0.7 and 8.1 ± 0.7 ng × islet 1 × 30 min 1 , and those from mGPDH-overexpressed GK rat islets 4.7 ± 0.3 and 9.1 ± 0.8 ng × islet 1 × 30 min 1 , in contrast to those from the Adex1-CAlacZ-infected non-diabetic Wistar rat islets (4.7 ± 1.6 and 47.6 ± 11.9 ng × islet 1 × 30 min 1 ). Thus, glucose-stimulated insulin secretion is severely impaired in GK rats even in the stage when mGPDH activity is modestly decreased, and at this stage, overexpression of mGPDH cannot restore glucose-stimulated insulin secretion. We conclude that decreased mGPDH activity in GK rat islets is not the defect primarily responsible for impaired glucose-stimulated insulin secretion. [Diabetologia (1998) 41: 649±653]

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Section: Discussioncontrasting

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: : 649±653]mentioning

confidence: 99%

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Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets

et al. 1998

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“…Other studies using GK rats originating from local colonies have also documented an impaired insulin secretory response [7,8]. Nevertheless it was claimed that such impairment in the London colony was not related to a reduced pancreatic insulin content [8], whereas decreased as well as normal pancreatic insulin content, together with normal islet beta-cell density, have been reported in adult GK rats in the Stockholm colony [7,9,10]. These conflicting data led us to document more extensively the beta-cell mass in GK rats originating from the Paris colony.…”

Section: Discussionmentioning

confidence: 99%

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

et al. 1997

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Established non-insulin-dependent diabetes mellitus (NIDDM) is associated with profound insulin secretory defects that occur together with insulin resistance. The basis for the insulin secretory defects is unknown and is difficult to study in human subjects because it is not possible to identify prospectively those subjects in whom glucose control will deteriorate. The fact that total beta-cell mass is decreased in NIDDM patients compared to weight-matched control subjects [1] offers strong support for the notion that insulin production may become insufficient if beta-cell growth is deficient. The contribution of decreased beta-cell mass to deficient insulin secretion Diabetologia (1997) 40: 916-925 Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

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“…Adv., 10 (9): 461-475, 2015 effect of CoQ10 is the glycerol-3-phosphate dehydrogenase (G3PD) shuttle. As G3PD is the rate-limiting in mitochondria can impact β-cell function in pancreas (Giroix et al, 1991;Ostenson et al, 1993;Sener et al, 1993;Fernandez-Alvarez et al, 1994). This G3PD activity was impaired diabetes condition (type II).…”

Section: Coenzyme Q10 On Blood Picturementioning

confidence: 99%

Dietary Essentiality I: Coenzyme Q10 Conditionally Essential-Review

Gopi¹,

Kumar²,

Elaiyaraja³

et al. 2015

Asian J. of Animal and Veterinary Advances

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The essentiality of nutrients keeps on changing with the advancement in nutritional research and genetic gain. The genetic gain especially in poultry sector is very high which results in increase in nutrient requirement of both the essential and non-essential nutrients. For the rapid growth the requirement of essential nutrients reaches many folds which are in direct relation with the performance, but the requirement for non-essential nutrients is an indirect one. Most of the dispensable amino acids, vitamin C, carnitine, etc. which are being synthesized endogenously are now a days unable to meet the birds requirements that warrants the dietary supply. Another important nutrient is coenzyme Q10 (CoQ10) which endogenously synthesized is now gaining much attention as a supplement for fast growing broilers. The CoQ10 can be termed as multi-functionary as each and every cell in the body needs this but quantity is being high for very active organs like heart, lungs, liver, kidney, etc. They are essential for cellular oxidative phosphorylation and regenerative antioxidant. The supplementation of CoQ10 improved the feed efficiency with reducing the electron leaks from mitochondria and increases total antioxidant capacity. For this property, CoQ10 is widely used in human medicine especially persons suffering from cardiac, neurological disorder, hypercholesterolemic condition and also even in cancer. The CoQ10 in poultry draws first attention when it is found to reducing the ascites mortality in marketable broilers. Thereafter, the advantages of CoQ10 is started to exploit with much attention to ascites, feed efficiency, cholesterol lowering effect nutraceutical and nutrigenomic property both in poultry and swine industry.

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Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats

Cited by 98 publications

References 24 publications

Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets

Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

Dietary Essentiality I: Coenzyme Q10 Conditionally Essential-Review

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