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...

Aims/Introduction Hyperglycemia is a risk factor for sarcopenia when comparing individuals with and without diabetes. However, no studies have investigated whether the findings could be extrapolated to patients with diabetes with relatively higher glycemic levels. Here, we aimed to clarify whether glycemic control was associated with sarcopenia in patients with type 2 diabetes. Materials and Methods Study participants consisted of patients with type 2 diabetes (n = 746, the average age was 69.9 years) and an older general population (n = 2,067, the average age was 68.2 years). Sarcopenia was defined as weak grip strength or slow usual gait speed and low skeletal mass index. Results Among patients with type 2 diabetes, 52 were diagnosed as having sarcopenia. The frequency of sarcopenia increased linearly with glycated hemoglobin (HbA1c) level, particularly in lean individuals (HbA1c <6.5%, 7.0%, ≥6.5% and <7.0%: 18.5%; HbA1c ≥7.0% and <8.0%: 20.3%; HbA1c ≥8.0%: 26.7%). The linear association was independent of major covariates, including anthropometric factors and duration of diabetes (HbA1c <6.5%: reference; ≥6.5% and <7.0%: odds ratio [OR] 4.38, P = 0.030; HbA1c ≥7.0% and <8.0%: 4.29, P = 0.024; HbA1c ≥8.0%: 7.82, P = 0.003). HbA1c level was specifically associated with low skeletal mass index (HbA1c ≥8.0%: OR 5.42, P < 0.001) rather than weak grip strength (OR 1.89, P = 0.058) or slow gait speed (OR 1.13, P = 0.672). No significant association was observed in the general population with a better glycemic profile. Conclusions Poor glycemic control in patients with diabetes was associated with low muscle mass.

The significance of the minimal secretory capacity of pancreatic beta-cells for the stability of the plasma glucose level was studied in 20 patients with insulin-dependent diabetes mellitus. Changes in plasma concentrations of major counterregulatory hormones in response to hypoglycemia were also investigated in these patients to clarify their contribution to diabetic brittleness. beta-Cell function was evaluated on the basis of elevation of plasma C-peptide immunoreactivity (CPR) during the intravenous glucagon test with a highly sensitive assay for plasma CPR that could detect as little as 0.03 ng/ml. After stimulation with glucagon, a significant increase in plasma CPR was observed in 10 of the patients whose beta-cell function had been evaluated as completely depleted by a conventional assay for plasma CPR. A clear inverse correlation was found between the secretory capacity of pancreatic beta-cells measured in this way and the degree of glycemic instability (r = -.74, P less than .01). Infusion of insulin at a rate of 0.15 U.kg-1.h-1 for 60 min caused a continuous decrease in the plasma glucose level, resulting in neuroglycopenia in 7 of the 10 CPR nonresponders but only 2 of the CPR responders. During insulin-induced hypoglycemia, plasma glucagon immunoreactivity did not increase in the CPR nonresponders but increased significantly in the CPR responders. A positive correlation was found between the minimal residual beta-cell capacity and the responsiveness of alpha-cells to hypoglycemia (r = .65, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Luseogliflozin treatment brought about favorable changes in body composition and metabolism of moderately obese Japanese type 2 diabetes patients, accompanied by body fat reduction, and minimal muscle and BMC reduction.