PARATHYROID-HORMONE DECREASES IN-VIVO INSULIN EFFECT ON GLUCOSE-UTILIZATION

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulin-mediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1-34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3 +/- 0.2 versus 9.9 +/- 0.1 mg/dl, P < 0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166 +/- 4 versus 155 +/- 4 mg/dL, P < 0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5 +/- 0.6 versus 5.6 +/- 0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205 +/- 13 versus 173 +/- 9; P < 0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05 +/- 0.3 versus 4.63 +/- 0.8; P = 0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r = 0.6, P = 0.02; r = 0.7, P = 0.01) and with the area under the glucose curve (r = 0.6, P = 0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P = 0.07) and 20-minute (P = 0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we Suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.