The purpose of this study was to identify the relationship between basal hepatic glucose production (HGP) and peripheral insulin sensitivity as assessed by the hyperinsulinemic euglycemic clamp prior to and during the development of non-insulin-dependent (type 2) diabetes mellitus in rhesus monkeys. Twenty-six male monkeys (Macaca mulatta), including normal animals and monkeys in various phases of the development of spontaneous obesity-associated type 2 diabetes were studied. Fasting plasma glucose (FPG) and insulin (FIRI), basal HGP using a [3H]glucose infusion, and peripheral insulin sensitivity (as determined by the euglycemic clamp technique) were examined. The earliest change that could be detected was a significant reduction in peripheral insulin sensitivity accompanied by increased FIRI. These changes preceded a significant deterioration of glucose tolerance. Basal HGP changed in parallel with FPG (r = 0.90, P less than 0.001), becoming significantly elevated only when FPG rose to levels diagnostic of diabetes (greater than 140 mg/dl). Thus basal HGP and fasting glucose levels showed no significant changes early in the development of type 2 diabetes. We conclude that the early serial decreases in insulin sensitivity and progressive increases in FIRI, with or without decreased glucose tolerance, are prognostic of the future development of diabetes in obese monkeys, a longitudinal process that is also likely to be observed in most if not all obese humans progressing to diabetes.

No abstract

Given the brain's capacity to recover from injury, plasticity may be enhanced following cerebral ischemia through environmental manipulation. Thus, the purpose of this study was to (1) determine the effects of early exposure to an enriched environment following ischemia on functional plasticity and (2) examine the relationship between morphological and behavioral plasticity. Adult female rats (n = 38) were divided into ischemia and control groups. Each group was further randomized to either standard (SC) or enriched conditions (EC). After 4 days of environmental exposure, rats were tested for 6 days in the water maze. Control and ischemia rats exposed to EC have increased total dendritic length (P < 0.05) as well as increased number of dendritic segments in the apical (P < 0.05) region of the hippocampal area compared to those housed in SC; furthermore, increased dendritic spine density in the apical (P < 0.05) region was also seen. Behavioral testing showed that ischemia rats exposed to SC have longer swim latencies (P < 0.05) and greater directional heading errors (P < 0.05) than ischemic rats exposed to EC; the latter group performed similar to controls. It is concluded that EC may be a potentially useful therapy in the recovery of spatial memory impairments seen after ischemia.