Insulin secretion in the obese (ob/ob) mouse. The effect of oxytetracycline on insulin release

The effect of oxytetracycline (OTC) pretreatment on the response of the ob/ob mouse to insulin secretagogues in vivo and in vitro was investigated. With glucose loading in vivo, the peak glucose was twofold greater and the insulin levels threefold greater in obese than in lean mice. After OTC treatment, there was no significant difference an insulin levels between lean and obese mice although the peak glucose level was still obese mice although the peak glucose level was still 1.5 times as high. Glucagon increased plasma glucose 2.5-fold and plasma insulin 20-fold in the obese as compared with lean mice. After OTC treatment the glycemic response of the obese was indistinguishable from that of the lean control. The insulin levels, while higher than those of lean mice, were only 25% of those found in the untreated obese. Aminophylline produced an 8- and a 20-fold increase in peak glucose and insulin levels, respectively, as compared with lean mice. In the OTC-treated obese mice, the injection of aminophylline produced a slower rise in plasma glucose than in the obese controls, but the levels were not significantly different from those of the untreated obese mice at 90 min. On the other hand, the insulin levels attained a plateau at a value which was one-fifth that found in the control obese group. In vitro, isolated islets from obese mice showed an exaggerated response to the secretagogues. Pretreatment with OTC attenuated this response. The fraction of insulin released at 10 mM glucose was less than one-fourth that in the obese controls.(ABSTRACT TRUNCATED AT 250 WORDS)