Regulation of obesity and insulin resistance by nitric oxide

Normal subjects and patients with adult-onset diabetes received 10 gm. of aspirin in four days. On the fourth day, the fasting serum glucose and the glucose response to oral glucose were decreased in both groups. These changes were associated with increased levels of serum insulin and pancreatic glucagon, although the glucagon responses to oral glucose were unchanged. In the diabetic patients, aspirin therapy was followed by a decreased glucose response to I.V. glucose and by the appearance of an early insulin peak, which could not be demonstrated before treatment. Aspirin did not affect the I.V. glucose tolerance in normal subjects, although it did enhance the early insulin peak. A decrease in the fasting levels of free fatty acids was noted in both groups, whereas the fasting level of triglycerides decreased only in the diabetic patients. Cholesterolemia did not change in either group. A few preliminary observations indicate that, in normal subjects, ibuprofen and ketoprofen, two other presumed prostaglandin inhibitors, did not affect fasting glycemia, glucose tolerance, or the insulin response to glucose. No changes were noted after the administration of placebo.

Aspirin Stimulates Insulin and Glucagon Secretion and Increases Glucose Tolerance in Normal and Diabetic Subjects

Salicylates lower blood sugar and enhance glucose-stimulated insulin secretion in normal and diabetic man. Although the hypoglycemic effect appears to be mediated by enhanced insulin secretion, extrapancreatic mechanisms cannot be excluded. The mechanism of the enhanced insulin secretion appears to be mediated by prostaglandin synthesis inhibition. The effect of salicylates on insulin secretion mediated by other secretagogues is imprecisely known. In addition to their glucose lowering action, salicylates have been reported to lower free fatty acids, triglycerides, and cholesterol. Salicylates have been imprecisely evaluated as hypoglycemic and hypolipidemic agents. Knowledge of their mechanism of action may provide further insight into the pathogenesis of diabetes mellitus and hyperlipidemic states.

Salicylates as Hypoglycemic Agents

Publisher Summary The salicylates are age old drug that in the form of willow bark and other herbal preparations have been used for long and their therapeutic effects have been reported in man first rather than in animals. It is suggested that salicylic acid was first used clinically in place of carbolic acid to disinfect wounds. When aspirin was introduced, as a more palatable and less topically toxic form of salicylic acid, the therapeutic properties of the parent compound were already well known. Because aspirin is probably the most widely used medicinal drug in the world, it is the mainstay of several pharmaceutical manufacturers. Interest lies in areas like what are the pharmacologic relatives of aspirin, where do the boundaries of this group of drugs lie, and does aspirin differ from sodium salicylate in its quantitative profile of actions. In view that aspirin is effective in its own right, this chapter explains the pharmacology of aspirin rather than that of salicylate in general. Results obtained with salicylates other than aspirin is only included, insofar, as they help to throw light on the pharmacology of aspirin. The chapter in the analysis of the antidefensive action of aspirin, considers the responses to noxae under various heads— namely, antipyresis, antinociception, anti-inflammation, antagonism of smooth muscle responses, and antihemostasis. The chapter also considers the other effects of aspirin that might be deemed antidefensive, such as damage to epithelia. When these pharmacologic effects of aspirin have been considered separately, how aspirin exerts these effects and to what extent a common mechanism underlying defensive responses may be identified as the target of this drug is assessed.

A Pharmacological Analysis of Aspirin

/pdf/salicylates-and-thyroid-function-i-depression-of-thyroid-1ticd25qaz.pdf

Salicylates and Thyroid Function. I. Depression of Thyroid Function

Large doses of salicylates have been reported to prevent diabetic glycosuria inman and the drug was used in the treatment of diabetes during the latter part of the last century (Gross & Greenberg, 1948). The recent report of Ingle (1950) that aspirin reduced the glycosuria of rats made mildly diabetic by partial pancreatectomy stimulated us to investigate this effect in more detail. In the present work the effect of salicylate on the glycosuria, blood glucose and liver glycogen of rats made severely diabetic with alloxanwas studied. The blood glucose and liver glycogen of normal rats treated with salicylate were also investigated because LutwakMann (1942) reported a marked decrease in liver glycogen in such animals.

/pdf/the-effect-of-salicylate-on-glycosuria-blood-glucose-and-24k52c7kku.pdf

J. Bornstein

Papers

The effect of salicylate on glycosuria, blood glucose and liver glycogen of the alloxan-diabetic rat.