The role of islet secretory function in the development of diabetes in the GK Wistar rat

Hughes, Stephen J.; Suzuki, K.; Goto, Y.

doi:10.1007/s001250050189

Cited by 13 publications

(21 citation statements)

References 22 publications

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“…In islets from GK rats, in our hands arginine was a poor stimulator of insulin secretion. This is in variance to findings by and Hughes et al (1994); we assume this to be related to differences between various GK rat colonies (CG Ö stenson, Stockholm, personal communication). In contrast, a strong synergistic interaction was observed in islets isolated from diabetic GK rats.…”

Section: Discussioncontrasting

confidence: 54%

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic β‐cells

Kaiser

Нешер

Oprescu

et al. 2005

British J Pharmacology

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1 S 21403 (mitiglinide) is a new drug for type 2 diabetes mellitus (T2DM). Its action on insulin release and biosynthesis was investigated in several experimental systems utilizing pancreas from normal and T2DM animals. 2 At high concentrations (10 mM), S 21403, like classical sulphonylurea, induced insulin release in the absence of glucose. In contrast, at therapeutic (0.1-1.0 mM) concentrations, S 21403 amplified insulin secretion glucose dose-dependently and with similar magnitude in normal and diabetic GK rat islets. 3 In perfused GK rat pancreas, S 21403 induced normal kinetics of insulin secretion including firstphase response. 4 The effect of S 21403 was strongly modulated by physiological factors. Thus, 0.1 mM adrenaline inhibited S 21403-induced insulin release. There was marked synergism between S 21403 and arginine in GK rat islets, combination of the two normalizing insulin secretion. 5 In primary islet cultures from normal rats or prediabetic Psammomys obesus, prolonged exposure to S 21403 did not induce further depletion of insulin stores under normal or 'glucotoxic' conditions. 6 Proinsulin biosynthesis was not affected by 2-h exposure of rat or prediabetic P. obesus islets to 1 mM S 21403. Yet, 24-h exposure of rat islets to S 21403 resulted in 30% increase in proinsulin biosynthesis at 8.3 mM glucose. 7 Amplification by S 21403 of glucose-induced insulin secretion in diabetic GK b-cells with restoration of first-phase response, a strong synergistic interaction with arginine and marked inhibition by adrenaline, make it a prime candidate for successful oral antidiabetic agent.

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Section: Discussioncontrasting

confidence: 54%

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic β‐cells

Kaiser

Нешер

Oprescu

et al. 2005

British J Pharmacology

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“…There is significant evidence for the role of glucose oxidation in insulin secretion, [38][39][40][41] and pregnancy increases the glucose oxidation rate. 14 Our data demonstrate that normal pregnancy increased the oxidation rate in islets that were exposed to either aforementioned glucose concentration and improved the glucose sensitivity of the islets.…”

Section: Discussionmentioning

confidence: 99%

A low‐protein diet during pregnancy alters glucose metabolism and insulin secretion

Souza

Ignácio-Souza

Reis

et al. 2011

Cell Biochemistry & Function

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In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events.

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“…This assumption is supported by the fact that glucokinase/hexokinase activities were normal in GK rat islets [14,30]. In addition, glycolytic rates in GK rat islets have been unchanged or increased compared with control islets [10,21,26,29,31,32]. Moreover, oxidation of glucose has been reported decreased [21], unchanged [10,26,29,31] or even enhanced [32].…”

Section: Islet and β‐Cell Functionmentioning

confidence: 98%

“…As GK rats originated from Wistar rats, this strain, preferably of out‐bred origin, has been used as control animals by most investigators. The body weights of adult GK rats are typically 10–30% lower than those of age‐matched control animals [10–12].…”

Section: The Gk Ratmentioning

confidence: 99%

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Islet gene expression and function in type 2 diabetes; studies in the Goto‐Kakizaki rat and humans

Östenson

Efendić

2007

Diabetes Obesity Metabolism

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Defective b-cell function with resulting impairment of glucose-stimulated insulin release is a critical factor in the pathogenesis of type 2 diabetes. Accumulated studies in pancreatic islets of the spontaneously diabetic GotoKakizaki (GK) rat suggest that this is a useful animal model of type 2 diabetes. The GK rat is non-obese, and abnormal glucose regulation develops early in life in association with impaired insulin secretion. There are some differences in islet morphology and function reported between different GK rat colonies. In addition to reduction of b-cell mass, a number of b-cell defects have been described with possible relevance for the reduced insulin secretion. Interestingly, some of these defects have also been shown in isolated islets from type 2 diabetic humans. The polygenic nature of diabetes heredity in the GK rat may well resemble the genetic basis in the majority of patients with type 2 diabetes. Here, we review studies concerning b-cell function and islet gene expression in the GK rat and compare it with the limited number of investigations on similar topics in isolated islets from patients with type 2 diabetes.

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The role of islet secretory function in the development of diabetes in the GK Wistar rat

Cited by 13 publications

References 22 publications

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic β‐cells

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic β‐cells

A low‐protein diet during pregnancy alters glucose metabolism and insulin secretion

Islet gene expression and function in type 2 diabetes; studies in the Goto‐Kakizaki rat and humans

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