The adrenergic regulation of lipolysis was investigated in situ at rest and during standardized bicycle exercise in nonobese healthy subjects, using microdialysis of the extracellular space in subcutaneous adipose tissue. The glycerol concentration was about two times greater in adipose tissue than in venous blood. At rest, the glycerol concentration in adipose tissue was rapidly increased by 100% (P < 0.01) after the addition of phentolamine to the ingoing perfusate, whereas addition of propranolol did not alter the adipose tissue glycerol level. Glycerol in adipose tissue and plasma increased during exercise and decreased in the postexercise period. Propranolol in the perfusate almost completely inhibited the increase in the tissue dialysate glycerol during the exercise-postexercise period. Phentolamine, however, was completely ineffective in this respect. During exercise, the lipolytic activity was significantly more marked in abdominal than in gluteal adipose tissue; this was much more apparent in women than in men. Thus, in vivo lipolysis in subcutaneous adipose tissue is regulated by different adrenergic mechanisms at rest and during exercise. Alphaadrenergic inhibitory effects modulate lipolysis at rest, whereas beta-adrenergic stimulatory effects modulate lipolysis during exercise. In addition, regional differences in lipolysis are present in vivo during exercise, which seem governed by factors relating to sex. (J. Clin. Invest. 1990. 85:893-898.) fat cell * glycerol . catecholamines

1 The effect of verapamil on the intestinal absorption of calcium was studied using a single isotope technique. Serum calcium and urinary excretion of calcium in the urine were followed in nine patients during treatment with verapamil for 2 months. 2 A dose of 80-120 mg (three times daily) resulted in a significant reduction of systolic and diastolic blood pressure.

In rats, verapamil decreases intestinal absorption of calcium, increases serum parathyroid hormone (PTH), and induces osteopenia. In this prospective study, verapamil 80-120 mg three times daily was given for 2 months to 20 patients with hypertension, and the effects on calcium homeostasis were recorded. This dose of verapamil significantly reduced supine systolic and diastolic blood pressure (+/- SD) from 158/100 +/- 9/8 mmHg to 146/89 +/- 14/8 mmHg (P = 0.001). Serum alkaline phosphatase (ALP) increased significantly from 2.77 +/- 1.06 mu kat l-1 to 3.19 +/- 1.22 mu kat l-1 (P = 0.004), and isoenzymes of ALP of skeletal origin appeared after verapamil treatment. The excretion of sodium in the urine increased (Na/creatinine ratio 8.95 +/- 6.01 before and 13.16 +/- 8.26 after verapamil; P = 0.04), while the excretion of calcium, phosphate and potassium was not changed. PTH was slightly increased at the end of verapamil treatment (1.09 +/- 0.54 vs. 0.98 +/- 0.74 microgram l-1; P = 0.07), and s-1,25(OH)2D3 was also somewhat increased (22.3 +/- 14.4 vs. 17.6 +/- 4.9 ng l-1; P = 0.26). Serum Ca was not affected by verapamil (before verapamil 2.43 +/- 0.11 mmol l-1, after verapamil 2.40 +/- 0.12 mmol l-1; P = 0.28). The increase in serum ALP demonstrates that verapamil affects bone cell metabolism in man. This effect could be secondary to the enhancement of PTH secretion.

The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean +/- SD of 1.10 +/- 0.06 to 1.24 +/- 0.38 mmol l-1; P less than 0.05), as well as total serum calcium corrected for protein (from 2.11 +/- 0.13 to 2.18 +/- 0.13 mmol l-1; P less than 0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 +/- 0.15 to 1.19 +/- 0.20 mmol l-1 P less than or equal to 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22 +/- 0.69 to 1.83 +/- 0.97; P less than or equal to 0.05). The serum 1,25-dihydroxyvitamin-D3 and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 +/- 0.70 before treatment and 1.25 +/- 0.71 micrograms l-1 after treatment). Thus in patients with post-surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil affects bone mineral metabolism.