DIETARY-TREATMENT AMELIORATES OVERT DIABETES AND DECREASED INSULIN-SECRETION TO GLUCOSE, INDUCED BY OVEREATING IN IMPAIRED GLUCOSE TOLERANT MICE

Overt diabetes (NIDDM) was induced by overeating in neonatally streptozocin (60 mg/kg·BW) treated impaired glucose tolerant mice. We imposed a food restriction and a high fiber diet to evaluate the effects of dietary treatment in this NIDDM model mouse. Furthermore, insulin secretion after the dietary treatment was studied using the perfused pancreas technique. One group of IGT mice (SZ) was maintained on ordinary mouse chow during 6 to 14 weeks of age. The others received a cookie and chocolate mashed diet (C.C. diet) to induce overt diabetes during 6 to 10 weeks of age. Thereafter, the mice with induced overt diabetes were divided according to their diet treatment. The C.C. diet was continued in one group (SZC) for 4 weeks, and the others were divided into a food restriction group (SZR: 4 g/mouse/day or ordinary mouse chow, for 4 weeks) and a high fiber diet group (SZF: 20% W/W of cellulose in ordinary mouse chow, for 8 weeks). The mean caloric intake/mouse/day in SZC, SZR and SZF were 140, 80 and 98% of that in SZ, respectively. Amelioration of hyperglycemia and impaired glucose tolerance was noted in SZR and SZF. A better glycemic control was obtained in SZF with keeping a normal growth rate. On the pancreas perfusion, the insulin secretion to 30 mM glucose was improved in SZR and SZF. Furthermore, the incremental first phase peak insulin release to 30 mM glucose in SZF was significantly greater than that in SZC (SZF, 10.5 ± 1.0 vs. SZC, 4.5 ± 1.9 μU/min). We conclude that these dietary treatments in this NIDDM model mouse ameliorate the glycemic control and the pancreatic β-cell insensitivity to glucose. An appropriate caloric intake with fiber enriched diet would produce a better glycemic control in diabetics. Furthermore, we proposse that the decreased first phase insulin to glucose may be a secondary manifestation of chronic hyperglycemia.