Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33±1 yr, body mass index 23.7±0.8 kg/ mI, blood pressure 146±3/97±3 mmHg, Vo2, v 37±3 ml/ kg per min) and 14 normal subjects (29±2 yr, 22.5±0.5 kg/M2, 118±4/69±3 mmHg, 43±2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155±15 g) and the normotensive (164±13 g) subjects. In the hypertensives, both whole body (28±3 vs 44±3 jamol/kg per mim P < 0.01) and femoral (64±11 vs 94±8 ,umol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939±51 vs 707±46 jzmol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulinstimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy. (J. Clin. Invest. 1995Invest. . 96:1003Invest. -1009.) Key words: insulin resistance * hypertrophy l left ventricle tomography

Exercise is known to decrease insulin secretion, but the effect on insulin clearance is unclear. We examined the effect of exercise in insulin clearance with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run (n = 14) or 44 h after a 2-h treadmill exercise (n = 14), and in seven insulin-dependent diabetes mellitus (IDDM) patients 12 h after a marathon run, and after a resting, control day. During the post-exercise insulin infusion, steady-state plasma insulin concentration was reduced by 9% in healthy men after both types of exercise, and by 16% in the diabetic subjects compared with the control study (P < 0.05 in all). In healthy men, C-peptide concentrations were more than one-third lower during insulin infusion, both after the marathon run (P < 0.001) or treadmill exercise (P < 0.02) compared with the control study. Insulin clearance was significantly increased by exercise both in healthy men (9% P < 0.05) and in IDDM subjects (15%, P < 0.05). After exercise, endogenous insulin secretion in healthy men is reduced and insulin clearance is enhanced both in healthy men and in IDDM patients. Decreased insulin availability may allow enhanced muscle lipid utilization and spare glucose after long-term exercise.

To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in UAG level was associated with improved insulin sensitivity via mechanisms independent of weight loss during an intensive, long-term exercise intervention in young healthy men.

Objective: Ghrelin, a gut-brain peptide involved in energy homeostasis, circulates predominantly (O90%) in unacylated form. Previous studies, however, have focused on total and acylated ghrelin, and the role of unacylated ghrelin (UAG) is not well understood. Particularly, the association of UAG with weight loss and changes in body composition in adults remains unclear. We hypothesized that exercise-associated increase in UAG level is associated with weight loss, favorable changes in body composition, and body fat distribution. Design and methods: A prospective study of 552 young men (mean age 19.3 and range 19-28 years) undergoing military service with structured 6-month exercise training program. Exercise performance, body composition, and biochemical measurements were obtained at baseline and follow-up. Association between changes in UAG levels and body composition and body fat distribution were evaluated. Results: An increase in UAG level during the exercise intervention was associated with reduced weight, fat mass (FM), fat percentage (fat %), and waist circumference, but not with fat-free mass. Inverse associations of changes in UAG level with changes in waist circumference and fat % were independent of weight at baseline, and changes in weight and exercise performance. Associations of changes in UAG level with waist circumference were significantly stronger than with fat % after the adjustment for confounding variables. Conclusion: UAG is associated with changes in body weight and body composition during an intensive long-term exercise intervention in young men. The association of UAG levels with changes in central obesity was stronger than with total FM.