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

Abstract

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...

A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2

“…We are surprised that there is not compensation for insulin deficiency with the single copy of Ins1 and with two copies of Ins1. However, a strain derived from the same colony as the NOD mouse, the NagoyaShibata-Yasuda mouse [9,10], a model of type 2 diabetes, which may share background genome with NOD [11,12], has no compensational hypertrophy of pancreatic islets despite increasing insulin resistance with ageing [9]. In addition, Kulkarni et al reported the importance of background genome in the induction of type 2 diabetes [13].…”

“…We believe that greater insulin resistance for male mice with marginal insulin production leads to hyperglycaemia. In fact, most animal models of type 2 diabetes (including NagoyaShibata-Yasuda mice) show a high prevalence of type 2 diabetes in male mice [9,10].…”

Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control

“…Tests of glucose metabolism in type 2 diabetes NSY mice Male NSY mice weighing 25-28 g were purchased from Japan SLC (Hamamatsu, Japan) [21]. A single mouse was housed per cage, with a light-dark cycle of 12 h each (light from 07.00-19.00 h), and free access to food and water.…”

“…d Atorvastatin treatment at days 1-5 of culture reduced levels of the adipocyte differentiation-related transcription factors PPARγ and C/EBPα, and these effects were partially prevented by co-administration of 10 μmol/l GGPP we next examined the possible impact of these effects on in vivo glucose metabolism using NSY mice. This mouse reportedly exhibits moderate levels of obesity, insulin resistance and impaired insulin response to glucose [21], and is therefore considered a model for human type 2 diabetes. We placed NSY mice on regular diet (control group) or one containing atorvastatin (ATR group) from 5-20 weeks of age.…”

Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of Type II diabetes mellitus; NSY mouse

“…The NSY mouse closely mimics human Type II diabetes in that the onset is agedependent, the animals are not severely obese, and both insulin resistance and impaired insulin response to glucose contribute to disease development [7]. Impaired insulin response to glucose is observed after 12 weeks of age in this strain, and this impairment progressively worsens with advancing age [7]. Although impaired insulin response to glucose seems to play an important part in the development of Type II diabetes in this strain, impaired insulin action possibly also contributes to glucose intolerance.…”