The spontaneous-diabetes rat: A model of noninsulin dependent diabetes mellitus.

Gotō, Yoshio; Kakizaki, Masaei

doi:10.2183/pjab.57.381

Cited by 128 publications

(95 citation statements)

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“…Further studies, in progress, are required to document whether a comparable enzymatic defect is present in the islets of GK rats. Meanwhile, our findings reveal that a preferential perturbation of oxidative glycolysis in pancreatic islets represents a metabolic feature of non-insulin-dependent diabetes not only in adult rats injected with streptozotocin during the neonatal period (STZ rats) but also in diabetic GK rats obtained by selective breeding over numerous generations [3,4]. Therefore, the preferential perturbation of oxidative glycolysis could conceivably represent a mechanism leading to spontaneous, as distinct from drug-induced, non-insulin-dependent diabetes.…”

Section: Discussionmentioning

confidence: 70%

“…at the level of its phosphorylation or oxidative catabolism. The present report reveals that, in two experimental models of non-insulin-dependent diabetes, namely in adult rats injected with streptozotocin during the neonatal period (STZ rats) and in spontaneously glucose-intolerant rats [3,4] obtained by selective breeding over numerous generations (GK rats), the oxidation of D-[3, 4-14C]glucose by pancreatic islets is impaired even when expressed relative to total glycolytic flux. Therefore, we propose that a perturbation of mitochondrial oxidative events, rather than hexose transport, plays an essential role in the secretory defect.…”

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confidence: 78%

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Preferential alteration of oxidative relative to total glycolysis in pancreatic islets of two rat models of inherited or acquired Type 2 (non-insulin-dependent) diabetes mellitus

Giroix

Sener²,

Portha

et al. 1993

Diabetologia

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Summary. In islets from both adult rats injected with streptozotocin during the neonatal period and spontaneously diabetic rats obtained by repeated selective breedings (GK rats), the ratio between D-[3, 4-14C]glucose oxidation and D-[5-3H]glucose conversion to 3HOH was 25 % lower than in islets from control rats, indicating an impaired contribution of oxidative to total glycolysis. No primary defect in the Krebs cycle was found in the islets of diabetic rats, as judged from the ratio between either D-[2-14C]glucose or D-[6-~4C]glucose and D-[3, 4-~4C]glucose oxidation. Therefore, we propose that a preferential alteration of oxidative glycolysis in the pancreatic beta cell may contribute to the impairment of glucose-induced insulin release not only in a cytotoxic but also in a spontaneous model of non-insulin-dependent diabetes mellitus.Key words: Pancreatic islets, GK rats, streptozotocin, glucose metabolism.The impairment of glucose-induced insulin release in noninsulin-dependent diabetes mellitus has been suggested to be caused by a defect of D-glucose transport across the islet beta-cell plasma membrane [1,2]. It is also conceivable, however, that such an impairment is due to a more distal anomaly in D-glucose metabolism, e.g. at the level of its phosphorylation or oxidative catabolism. The present report reveals that, in two experimental models of non-insulin-dependent diabetes, namely in adult rats injected with streptozotocin during the neonatal period (STZ rats) and in spontaneously glucose-intolerant rats [3,4] obtained by selective breeding over numerous generations (GK rats), the oxidation of D-[3, 4-14C]glucose by pancreatic islets is impaired even when expressed relative to total glycolytic flux. Therefore, we propose that a perturbation of mitochondrial oxidative events, rather than hexose transport, plays an essential role in the secretory defect. Materials and methodsControl Wistar rats, animals injected with STZ [5] during the neonatal period (STZ rats) and GK rats [6] were given free access to food [7]. The rats were weighed and then decapitated. Blood was col~ lected in heparinized tubes for the measurement of plasma glucose by the glucose oxidase method [8] and plasma insulin by radioimmunoassay [9]. In each experiment, islets were isolated by the collagenase method [10] from the pancreas of two rats in each group. Two groups of ten islets each were used for the measurement of islet protein and insulin content [10,11]. For the measurement of t4C-labelled D-glucose oxidation and D-[5-3H]glucose utilization, groups of ten islets each were incubated for 120 min at 37 ~ in 40 gt of a bicarbonate-buffered medium [10] containing bovine serum albumin (5 mg/ml). In some experiments, the incubation medium was deprived of CaC12 and contained 0.5 mmol/1EGTA. The production of ~4CO2 and 3HOH was measured as previously described [12]. The acidified medium containing the islets was stored at -20 ~ and later examined for its content in z4C-labelled amino acids and acidic metabolites separated by ion-exchan...

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 78%

Preferential alteration of oxidative relative to total glycolysis in pancreatic islets of two rat models of inherited or acquired Type 2 (non-insulin-dependent) diabetes mellitus

Giroix

Sener²,

Portha

et al. 1993

Diabetologia

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“…Previous reports have shown progressive proliferation of fibrous tissue in the islets of GK rats, ultimately leading to the formation of irregularly shaped, so-called starfish islets, with a decreased number of -cells (Goto & Kakizaki 1981, Höög et al 1996. However, in previous investigations involving 8-week-old Wistar, GK and hybrid rats from the Stockholm colony, a majority of the islets appeared histologically normal and only a few starfishshaped islets were found (Abdel-Halim et al 1994, Guenifi et al 1995.…”

Section: Discussionmentioning

confidence: 91%

“…The GK (Goto-Kakizaki) rat is a non-obese animal model of hereditary non-insulin-dependent diabetes mellitus with mild hyperglycemia, initially derived from normal Wistar rats by repeatedly selecting animals with slightly aberrant glucose-tolerance tests for breeding (Goto & Kakizaki 1981, Kimura et al 1982, Suzuki & Goto 1987. The exact mechanism behind the impaired glucose-induced insulin release in the GK rat is unclear.…”

Section: Introductionmentioning

confidence: 99%

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Svensson

Östenson²,

Bodin³

et al. 2005

Journal of Endocrinology

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The effects of a 60% partial pancreatectomy were studied in hyperglycemic GK (Goto-Kakizaki) rats. Partial pancreatectomy or a sham operation was performed on 12-weekold female Wistar rats, GK rats or hybrids between male GK rats and female Wistar rats. Measurements of pancreatic blood flow and islet blood flow were performed by a microsphere technique 2 weeks after surgery. Glucose tolerance was decreased in hybrid compared with Wistar rats, and in GK rats compared with both hybrid and Wistar rats before surgery. Partial pancreatectomy induced minor changes in glucose tolerance. Wistar rats had a decreased islet mass following partial pancreatectomy. Both hybrid and GK rats showed a significant decrease in relative islet volume, but only GK rats in total islet mass, compared with Wistar rats 2 weeks after surgery. Pancreatic blood flow and islet blood flow did not significantly differ between sham-operated Wistar, hybrid or GK rats. After partial pancreatectomy, islet blood flow in relation to islet mass increased 3-fold in Wistar rats and 2-fold in hybrid rats. In contrast, GK rats showed no increase in islet blood flow following partial pancreatectomy. It is concluded that compensatory mechanisms after partial pancreatectomy are operating less efficiently in hybrid and GK rats.

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“…The GK rat is a spontaneously non-obese diabetic animal model, produced by selective inbreeding of Wistar rats presenting the highest glucose levels during the oral glucose tolerance test [44]. This animal model is characterised by β-cell mass reduction, β-cell dysfunction and insulin resistance leading to diabetes mellitus [40,45,46].…”

Section: Discussionmentioning

confidence: 99%

Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets

et al. 2007

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We investigated the effect of sub-chronic soybean oil (SO) treatment on the insulin secretion and fatty acid composition of islets of Langerhans obtained from Goto-Kakizaki (GK), a model of type 2 diabetes, and normal Wistar rats. We observed that soybean-treated Wistar rats present insulin resistance and defective islet insulin secretion when compared with untreated Wistar rats. The decrease in insulin secretion occurred at all concentrations of glucose and arginine tested. Furthermore we observed that soybean-treated normal islets present a significant decrease in two saturated fatty acids, myristic and heneicosanoic acids, and one monounsaturated eicosenoic acid, and the appearance of the monounsaturated erucic acid. Concerning diabetic animals, we observed that soybean-treated diabetic rats, when compared with untreated GK rats, present an increase in plasma non-fasting free fatty acids, an exacerbation of islet insulin secretion impairment in all conditions tested and a significant decrease in the monounsaturated palmitoleic acid. Altogether our results show that SO treatment results in a decrease of insulin secretion and alterations on fatty acid composition in normal and diabetic islets. Furthermore, the impairment of insulin secretion, islet erucic acid and fasting plasma insulin levels are similar in treated normal and untreated diabetic rats, suggesting that SO could have a deleterious effect on β-cell function and insulin sensitivity.

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The spontaneous-diabetes rat: A model of noninsulin dependent diabetes mellitus.

Cited by 128 publications

References 0 publications

Preferential alteration of oxidative relative to total glycolysis in pancreatic islets of two rat models of inherited or acquired Type 2 (non-insulin-dependent) diabetes mellitus

Preferential alteration of oxidative relative to total glycolysis in pancreatic islets of two rat models of inherited or acquired Type 2 (non-insulin-dependent) diabetes mellitus

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets

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