Risk factors for worsening to diabetes in subjects with impaired glucose tolerance

Kadowaki, Takashi; Miyake, Yumiko; Hagura, Ryoko; Akanuma, Yasuo; Kajinuma, Hiroshi; Kuzuya, Nobusada; Takaku, Fumimaro; Kosáka, Kinori

doi:10.1007/bf00252262

Cited by 306 publications

(210 citation statements)

References 24 publications

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“…In these patients, glucose-stimulated insulin secretion is selectively impaired, but near normal response to L-arginine has been reported [23,24]. In fact, impaired insulin response to glucose has been suggested to be an important predisposing factor for the development of glucose intolerance in patients with NIDDM [25,26].…”

Section: Discussionmentioning

confidence: 99%

The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity

et al. 1995

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SummaryThe NSY (Nagoya-Shibata-Yasuda) mouse was established as an inbred strain of mouse with spontaneous development of diabetes mellitus, by selective breeding for glucose intolerance from outbred Jcl:ICR mice. NSY mice spontaneously develop diabetes mellitus in an age-dependent manner. The cumulative incidence of diabetes is 98 % in males and 31% in females at 48 weeks of age. Neither severe obesity nor extreme hyperinsulinaemia is observed at any age in these mice. Glucose-stimulated insulin secretion was markedly impaired in NSY mice after 24 weeks of age. In contrast, fasting plasma insulin level was higher in male NSY mice than that in male C3H/He mice (545 +73 vs 350+ 40 pmol/1, p < 0.05, at 36 weeks of age). Pancreatic insulin content was higher in male NSY mice than that in male C3H/He mice (76 + 8 vs 52 _+ 5 ng/mg wet weight, p < 0.05, at 36 weeks of age). Morphologically, no abnormal findings, such as hypertrophy or inflammatory changes in the pancreatic islets, were observed in NSY mice at any age. These data suggest that functional changes of insulin secretion in response to glucose from pancreatic beta cells may contribute to the development of non-insulin-dependent diabetes mellitus (NIDDM) in the NSY mouse. Although insulin sensitivity was not measured, fasting hyperinsulinaemia in NSY mice suggests that insulin resistance may also contribute to the pathogenesis of NIDDM. Since these findings are similar to the pathophysiologic features of human NIDDM patients, the NSY mouse is considered to be useful for investigating the pathogenesis and genetic predisposition to NIDDM. [Diabetologia (1995) 38: 503-508] Key words NSY mouse, non-insulin-dependent diabetes mellitus, animal model, insulin secretion, isolated islets.Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder, caused by an interaction of genetic and environmental factors [1][2][3]. This heterogeneity in human NIDDM makes it difficult to clarify the genetics or pathogenesis of the disease. Animal models are invaluable for the analysis of heterogeneous disorders such as diabetes. This is eviReceived: 22 June 1994 and in revised form: 11 October 1994 Corresponding author: Dr. H. Ikegami, Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan Abbreviations: NIDDM, Non-insulin-dependent diabetes mellitus; IDDM, insulin-dependent diabetes mellitus; NSY mouse, Nagoya-Shibata-Yasuda mouse.denced by the recent progress in the understanding of the genetics and pathogenesis of insulin-dependent diabetes mellitus by use of excellent animal models, such as the nonobese diabetic (NOD) mouse and the Bio-Breeding (BB) rat [4]. Several animal models for NIDDM have been described. Although recent studies have revealed impaired insulin secretion in GK rats [5][6][7], most of the animal models for NIDDM are characterized by obesity, hyperinsulinaemia and islet hypertrophy [8].The NSY (Nagoya-Shibata-Yasuda) mouse is a spontaneous model of NIDDM with moderate obesity that was establ...

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Section: Discussionmentioning

confidence: 99%

The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity

et al. 1995

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“…Given the fact that diabetes develops when the insulin secretion by beta cells is insufficient to compensate for insulin resistance [22,23] and GLP-1 reportedly inhibits apoptosis in humans, the increase in the GLP-1 concentration may be important for improving beta cell function [24]. In addition, the increase in GLP-1 may protect against obesity because of the anti-obesity effect GLP-1 [25][26][27][28].…”

Section: A B a Bmentioning

confidence: 99%

Mosapride citrate, a 5-HT<sub>4</sub> receptor agonist, increased the plasma active and total glucagon-like peptide-1 levels in non-diabetic men

et al. 2013

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“…Loss of the first phase insulin response to intravenous glucose is a feature characteristic of pre-Type II diabetes [14]. It is not clear whether the abnormality is acquired or an intrinsic disturbance of insulin secretion regarded as necessary, though on its own not usually sufficient, to cause Type II diabetes.…”

Section: Pathophysiology Of Diabetesmentioning

confidence: 99%

The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes

2001

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Diabetes is currently of two types. Type I (insulin-dependent) diabetes mellitus is an autoimmune disorder of childhood, characterised by acute onset, ketoacidosis and insulin dependency. Type II diabetes is a metabolic disorder of middle-life, slow in onset and non-insulin-dependent.The definitions need urgent revision. More than half of the patients with Type I diabetes present in adulthood, when their onset is slow and many do not develop acidosis or require insulin for many years [1]. Type II diabetes occurs in teenagers [2], sometimes with keto-acidosis [3], and insulin-dependency frequently ensues given time. Clinically, there is little other than tempo to distinguish two types of diabetes. The HypothesisThe`Accelerator Hypothesis' argues that Type I and Type II diabetes are one and the same, distinguishable only by their rate of beta cell loss and the accelerators responsible. The first accelerator, a constitutionally (intrinsically) high rate of beta-cell apoptosis, is necessary for diabetes to develop but in itself rarely Diabetologia (2001) AbstractBlood glucose concentrations are controlled by a loop incorporating two components, the beta cells which secrete insulin and the insulin-sensitive tissues (liver, muscle, adipose) which respond to it. Loss of blood glucose control might result from failure of the beta cells to secrete insulin, resistance of the tissues to its action, or a combination of both. The distinctions between Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus are becoming increasingly blurred both clinically and aetiologically, where beta-cell insufficiency is the shared characteristic. The`Accelerator Hypothesis' identifies three processes which variably accelerate the loss of beta cells through apoptosis: constitution, insulin resistance and autoimmunity.None of the accelerators leads to diabetes without excess weight gain, a trend which the`Accelerator Hypothesis' deems central to the rising incidence of both types of diabetes in the industrially developed world. Weight gain causes an increase in insulin resistance, which results in the weakening of glucose control. The rising blood glucose (glucotoxicity) accelerates beta-cell apoptosis directly in all and, by inducing beta-cell immunogens, further accelerates it in a subset genetically predisposed to autoimmunity. Rather than overlap between two types of diabetes, the`Accelerator Hypothesis' envisages overlay. Body mass is central to the development and rising incidence of all diabetes. Only tempo distinguishes the`types'. The control of weight gain, and with it insulin resistance, could be the means of minimising both.

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Risk factors for worsening to diabetes in subjects with impaired glucose tolerance

Cited by 306 publications

References 24 publications

The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity

The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity

Mosapride citrate, a 5-HT<sub>4</sub> receptor agonist, increased the plasma active and total glucagon-like peptide-1 levels in non-diabetic men

The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes

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