[The mode of action of insulin (author's transl)].
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Biomedical subjects
Publications and source records attributed to J Zapf.
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Adipose tissue from streptozotocin-diabetic rats exhibits half-maximal lipolytic responses (FFA, glycerol release, increase in tissue FFA) to epinephrine at hormone concentrations 5-10 times lowere than those required for half-maximal stimulation of lipolysis in adipose tissue from normal rats. The lipolytic response to epinephrine also occurs more promptly and the antilipolytic effect of insulin in the presence of submaximal epinephrine conceptrations is much less pronounced than in normal tissue. In contrast, diabetic adipose tissue is less responsive to ACTH and glucagon than normal tissue. Half-maximal lipolytic responses are elicited by similar dibutyryl cyclic AMP concentrations in both tissues. Insulin treatment of diabetic rats during 24 hrs restores the lipolytic response of their adipose tissue to epinephrine to nearly normal. Our findings point to an abnormality of diabetic adipose tissue possibly related to the hypersensitivity of catecholamines encountered in denervated organs which are adrenergically innvervated. They are consistent with present concept of different hormone discriminators on the fat cell membrane and offer a further explanation for increased FFA mobilization in the diabetic state.
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Osteopenia and retarded skeletal growth are consistent features of juvenile polyarthritis. Although the former has also been described in the experimental animal, the consequences of induced joint inflammation on skeletal growth have not yet been documented. In order to investigate the effect of experimental arthritis on these parameters, we studied female rats with adjuvant arthritis (AA) subjected to chronic treatment with cyclosporin A (CsA, Sandimmun). This compound has been found to prevent the development of articular swelling and also repair joint and skeletal lesions in AA rats. Five groups of 8 animals each received oral CsA, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Eight normal and eight diseased, untreated rats served as placebo controls. The parameters studied were (a) measurement of hindpaw swelling, (b) radiometric assessment of vertebral growth, (c) vertebral trabecular density, (d) weight control and nutritional status. At the end of the investigational period, AA-rats on no therapy had severe osteopenia and growth retardation. Treatment with CsA, 2.5 mg/kg, was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions and normalized growth. A catch-up phenomenon was also observed. The 20 mg/kg dose showed no better effect than 10 mg/kg, and 30 mg/kg produced a significant reduction in bone density and skeletal growth, an effect thought to be toxic in nature. Body weight paralleled growth profiles, and average food consumption was stable in all groups with the exception of somewhat low records in the animals receiving 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)