The effect of oxytetracycline on insulin resistance in obese mice

Abstract

1. Chronic oxytetracycline treatment was found to improve the insulin resistance of the obese-hyperglycaemic mouse. 2. The improved response to insulin was accompanied by decreased concentrations of circulating insulin and glucose, by a decrease in the lipid content of the liver and by an increase in the insulin-receptor sites of the liver and adipose tissue. 3. The increase in insulin-receptor sites preceded the fall in blood glucose. 4. Comparable studies done on food-restricted animals indicated that although chronic food restriction corrected the hyperinsulinaemia it did not restore the insulin-receptor sites or the hyperglycaemia.The obese-hyperglycaemic mouse is characterized by obesity, non-ketotic hyperglycaemia, hyperinsulinism, islet-cell hyperplasia and resistance to exogenous insulin. Insulin resistance in the obesehyperglycaemic mouse has been attributed to several factors.(1) The number of insulin-binding sites on

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

“…7) insulin binding by hepatic plasma membranes from the ob/ob mouse (4,39), the db/db mouse (4), and the gold thioglucose rat (4), by adipocytes from the ob/ob mouse (39) and by monocytes from obese human subjects (11). The enhancement of insulin binding by caloric restriction in the ob/ob mouse can be prevented by administering exogenous insulin during this period (4).…”

“…The enhancement of insulin binding by caloric restriction in the ob/ob mouse can be prevented by administering exogenous insulin during this period (4). Treatment of the ob/ob mouse with oxytetracycline also decreases insulin levels and increases insulin binding by both hepatic plasma membranes and adipocytes (39). New Zealand obese mice have increased insulin concentrations and decreased binding by hepatic plasma membranes (33).…”

Age dependent effects of oxytetracycline in ob/ob mice

“…Since oxytetracycline has been shown to increase the in vitro insulin sensitivity of ob/ob mouse muscle, to "normalize" in vivo glucose and insulin tolerance in ob/ob mice [5,6], and to potentiate the effects of exogenous insulin in depancreatectomized dogs [7,8], the drug appears to act by increasing target cell sensitivity to the catalytic actions of insulin.…”

“…Earlier reports have demonstrated that the longterm administration of oxytetracycline to animals having either experimental diabetes or genetic diabetes-obesity results in a reduced severity of the diabetic symptoms [5][6][7][8]. Since oxytetracycline has been shown to increase the in vitro insulin sensitivity of ob/ob mouse muscle, to "normalize" in vivo glucose and insulin tolerance in ob/ob mice [5,6], and to potentiate the effects of exogenous insulin in depancreatectomized dogs [7,8], the drug appears to act by increasing target cell sensitivity to the catalytic actions of insulin.…”

“…As yet, it is not clear which of these abnormalities are direct expressions of the mutation, but examination of the early development of the obese-hyperglycaemic syndrome indicates that obesity, hyperinsulinaemia, hyperphagia, and reduced activity precede the occurrence of hypcrglycaemia and insulin resistance [2][3][4]. Recently, the antibiotic oxytetracycline (Terramycin) has been shown to normalize the hyperglycaemia, hyperinsulinaemia, and insulin resistance of mature ob/ob mice [5,6] and to potentiate the effects of exogenous insulin in the treatment of experimental diabetes mellitus in dogs [7,8]. Since, in these studies, the drug's effectiveness appeared to stem from a modification of tissue sensitivity to insulin, we examined the effects of oxytetracycline on the growth and in vivo metabolism of ob/ob mice: 1) during the early development of the syndrome when insulin resistance and hyperglycaemia have not yet appeared (17-28 days of age), 2) during the 'dynamic' phase of the syndrome when basal glucose levels reach peak values (10 weeks of age), and 3) during the late phase of the syndrome when glucose levels return toward normal but hyperinsulinaemia and insulin resistance persist (24 weeks of age).…”