SPECIFIC ADAPTATIONS IN MUSCLE AND ADIPOSE-TISSUE IN RESPONSE TO CHRONIC SYSTEMIC GLUCOSE OVERSUPPLY IN RATS

Specific adaptations in muscle and adipose tissue in response to chron ic systemic glucose oversupply in rats. Am. J. Physiol. 273 (Endocrino l. Metab. 36): E1-E9, 1997.-Rats minimize hyperglycemia during chronic glucose infusion, but the metabolic processes are unclear. We investi gated the tissues involved and the role of altered insulin sensitivity . Cannulated rats were infused with glucose (40 mg.kg(-1).min(-1)) for 1 or 4 days or with saline (control). Hyperglycemia at 1 day (15.3 +/ - 1.0 mM) was absent at 4 days (7.5 +/- 0.3 mM), but hyperinsulinemia persisted. Whole body glucose disposal was similarly elevated at 1 and 4 days, implying increased glucose clearance at 4 days (2-fold, P < 0 .001). Muscle glucose uptake and glycogen content declined in glucose- infused rats from 1 to 4 days, whereas white adipose tissue (WAT) gluc ose uptake (6-fold, P < 0.001) and lipogenesis (3-fold, P < 0.001)incr eased. Muscle and liver triglyceride were doubled at both 1 and 4 days (P < 0.05 vs. control). Insulin sensitivity (assessed during euglycem ic clamps) decreased in muscle to 34% of control at 1 and 4 days (P < 0.001 vs. control) and increased fivefold in WAT from 1 to 4 days (P < 0.05). Thus chronic glucose infusion results in a slow increase in ef ficiency of glucose clearance with enhanced WAT glucose uptake, lipoge nesis, and insulin action. In contrast, the adaptation reduces glucose oversupply to muscle. Muscle shows sustained insulin resistance, with lipid accumulation a possible contributing factor.