There is now considerable evidence that behavioral variables are important determinants of hyperglycemia in NIDDM. We have shown that the obese mouse, a common animal model of NIDDM, is not hyperglycemic unless exposed to stress; that hyperglycemia can be induced both acutely and chronically through a variety of behavioral manipulations and that stress-hyperglycemia can be attenuated with alprazolam - a benzodiazepine. Furthermore, we have demonstrated that a brief trial of relaxation training can significantly improve glucose tolerance in patients with NIDDM and we have gathered preliminary data to suggest that alprazolam also improves glucose tolerance in these patients. The research proposed for the next five year period of this RSDA will focus on furthering our understanding of the role of behavior in the expression of hyperglycemia in NIDDM. We will restrict our focus to NIDDM because we have already accumulated considerable evidence that stress plays a major role in at least one animal model of this condition and because research in our laboratory and elsewhere has suggested that relaxation training may improve glucose metabolism in NIDDM but not in NIDDM. Utilizing two animal models of NIDDM we will continue to explore the mechanism by which chronic stress can influence the course of hyperglycemia over an extended period and see if this stress response can be attenuated with benzodiazepine treatment. We will investigate the relationship of diet and obesity to the degree to which stress produces hyperglycemia in animals genetically predisposed to diabetes and we will study the relationship of controllability and predictability of aversive stimulation to the development of hyperglycemia. Finally, we will re-examine the use of relaxation training and benzodiazepine therapy in the treatment of NIDDM. We will attempt to determine the mechanism by which relaxation and alprazolam improve glucose metabolism and we will assess whether the observed therapeutic effects are long lasting. In the conduct of these investigations we will try to identify both physiologic and behavioral individual differences which predict successful outcome of behavioral and pharmacologic anxiolytic therapy in the treatment of NIDDM.