H. M. C. Heick

Zinc Supplementation Attenuates Insulin Secretory Activity in Pancreatic Islets of the ob/ob Mouse

The purpose of this study was to establish whether a relationship may exist between the hyperinsulinemia, the exaggerated insulin secretion, and the resistance to insulin characteristic of the obese-hyperglycemic syndrome and the zinc status of the ob/ob mouse. To this end, mice were given control and zinc-supplemented diets, and the effects of zinc supplementation on insulin secretion in vivo and in vitro as well as on glucose tolerance were studied. These data were compared with those obtained with oxytetracycline treatment, which is known to ameliorate the insulin sensitivity and glucose tolerance of these animals. The levels of zinc were measured in several tissues of lean and obese mice and the results show that zinc supplementation attenuated the exaggerated insulin secretion in vivo and in vitro without improving the tolerance to glucose. Zinc levels were significantly higher in the tissues of the obese than of the lean mice, with the exception of bone and pancreas. The results suggest a maldistribution of zinc in the tissues of the obese mouse.

Oxytetracycline Treatment Improves the Response to Insulin in the Spontaneously Diabetic (BB) Rat

Chronic oxytetracycline treatment was found to alter the diabetic status of the spontaneously diabetic rat (BB rat). The treatment led to lowered plasma glucose levels in the fed as well as in the fasted state. These results indicate that the oxytetracycline treatment was effective in lowering the insulin requirements as well as in improving the handling of glucose. The effects of the drug are not secondary to the decreased food intake as a food restricted control group did not show the improvements in glycemia or glucose and insulin tolerance. These results are a further indication that oxytetracycline enhances the response of peripheral tissues to insulin and thus favors better control of glycemia.

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 in insulin levels between lean and 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 glycemie 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. With glucagon added, the response was only one-eighth, and with aminophylline, one-half as great in the OTC-treated than in the obese control. The effects of OTC cannot be attributed to the effects of the drug on food consumption, since obese mice food restricted to the intake of the OTC-treated obese mice showed either no improvement or much smaller Changes.

Use of Beckman BUN analysers to determine urine urea

In this paper we report a method to enable the Beckman BUN analyser to be used for urine urea nitrogen determinations. Satisfactory urine samples could be obtained by diluting the urine with 10 volumes of 0.85% saline. We also report our experience with the use of reagent prepared in house and with a modified pipette, to reduce the cost of using the instrument.

Regranulation of Islets of Langerhans and Normalization of In Vivo Insulin Secretion in ob/ob Mice Treated with Oxytetracycline

Oxytetracycline (OTC) treatment was associated with regranulation of the islet cells and increased pancreatic insulin content in the ob/ob mouse. This was accompanied by an improvement of the in vivo insulin secretory response to glucose. Because of the wide-ranging effects of OTC on other membrane-related functions, it is postulated that this compound may exert its effect by altering the composition of cellular membranes.