The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.

OBJECTIVE: To determine the effects of excess carbohydrate or fat intake on plasma leptin concentrations and energy expenditure. DESIGN: Ten healthy lean females were studied: (a) during a 3 day isoenergetic diet (ISO); (b) during 3 day carbohydrate overfeeding (CHO OF); and (c) during 3 day fat overfeeding (FAT OF). During each test, basal metabolic rate, the energy expended during mild physical activity and recovery, and 24 h energy expenditure (24 h EE) were measured with indirect calorimetry. The concentrations of glucose and lactate were monitored in subcutaneous interstitial¯uid over a 24 h period using microdialysis. Plasma hormone and substrate concentrations were measured in a blood sample collected in the morning of the fourth day. RESULTS: CHO OF increased plasma leptin concentrations by 28%, and 24 h EE by 7%. Basal metabolic rate and the energy expended during physical activity were not affected. FAT OF did not signi®cantly change plasma leptin concentrations or energy expenditure. There was no relationship between changes in leptin concentrations and changes in energy expenditure, suggesting that leptin is not involved in the stimulation of energy metabolism during overfeeding. Interstitial subcutaneous glucose and lactate concentrations were not altered by CHO OF and FAT OF. CONCLUSIONS: CHO OF, but not FAT OF, increases energy expenditure and leptin concentration.

Recent work performed in the field has indicated that stress may be a significant factor in the pathogenesis of metabolic disorders. Nutritional intervention or pharmacological agents targeted at modulating stress should be investigated.

Mutations of HNF-1a lead to severe b cell dysfunction, resulting in decreased glucose-induced insulin secretion. HNF-1a is also expressed in liver, kidney and pancreatic a cells, but the functional consequences of HNF-1a mutations in these organs remain unknown. We therefore assessed the counterregulatory responses to hypoglycemia in six patients with HNF-1a mutations (MODY3), five patients with non-insulin-dependent diabetes mellitus (NIDDM) and in nine healthy controls. Plasma glucagon concentrations and endogenous glucose production were measured every 15 min during a hyperinsulinemic clamp with progressive hypoglycemia. Plasma glucagon concentrations were similar at basal glycemia 73^6Y 69^5 and 69^7 ngal and reached peak values of 88^9Y 88^11 and 89^7 ngal at a glycemia of 3.6 mmol/l in MODY3 patients, patients with NIDDM and controls respectively (NS). Suppression of endogenous glucose production by insulin was blunted in MODY3 patients 3X3^1X2 mmolakg per min) and in patients with NIDDM 4X4^0X6 mmolakg per min) compared with controls 1X7^0X5 mmolakg per min, P , 0X05 compared with both MODY3 patients and patients with NIDDM). During hypoglycemia, endogenous glucose production increased to 8X6^2X1Y 8X8^0X7 and 7X0^1X0 mmolakg per min in MODY3 patients, patients with NIDDM and controls respectively (all NS). These data indicate that mutations of HNF-1a in MODY3 do not result in a decreased glucagon secretion or alterations of glucose production during hypoglycemia.

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