Drugs online research references
Am J Med. 1983 Nov 30;75(5B):8-14.
Effect of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism in patients with noninsulin-dependent diabetes mellitus.
Reaven GM.
Glipizide is a "second generation" sulfonylurea compound, and in this study the effects of several months of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism were documented in 23 patients with noninsulin-dependent diabetes mellitus. Mean (+/-SEM) fasting plasma glucose concentration decreased (p less than 0.001) from 264 +/- 12 to 172 +/- 10 mg/dl, and a similar decrement in postprandial glucose concentration was also seen following glipizide therapy. Mean plasma triglyceride concentration was also lower (p less than 0.05) after glipizide treatment and was associated with modest reciprocal changes in plasma cholesterol (lower) and high-density lipoprotein cholesterol (higher) concentrations. Although neither of these latter two effects was statistically significant, the net effect was to lead to a significant (p less than 0.02) increase in the ratio of high-density lipoprotein cholesterol to total cholesterol. Furthermore, significant relationships were noted between the improvement in diabetic control in glipizide-treated patients and lowering of both very low-density lipoprotein-triglyceride (r = 0.69, p less than 0.001) and low-density lipoprotein-cholesterol (r = 0.54, p less than 0.02) concentrations. Finally, glipizide treatment was associated with improvements in both the plasma insulin response to mixed meals and estimates of in vivo insulin-stimulated glucose utilization. Although both of these changes were likely to have contributed to the ability of glipizide to lower plasma glucose concentrations, only the increase in in vivo insulin action correlated with the improvement in diabetic control (r = 0.69, p less than 0.001).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6369970&dopt=Abstract
Diabetes Care. 1984 May-Jun;7 Suppl 1:42-6.
Sulfonylurea effects on target tissues for insulin.
McCaleb ML, Maloff BL, Nowak SM, Lockwood DH.
We have examined the nonpancreatic actions of sulfonylureas on multiple aspects of insulin responsiveness in two target tissues for insulin, liver and fat. In vivo administration of tolazamide and glipizide reduced significantly the postabsorptive serum glucose levels in rats without altering the levels of insulin. This was consistent with extrapancreatic sites of drug action. The number and affinity of hepatic insulin receptors was not different from those of control rats. Using a tissue culture system for rat adipose tissue, a 20-h treatment with sulfonylureas markedly potentiated insulin action in fat cells. The primary augmentation was at the level of insulin-stimulated glucose transport. Again, there was no alteration of the insulin receptors located on the adipose tissue. Furthermore, consistent with the lack of an influence on insulin-induced receptor loss after in vitro treatment with sulfonylureas, the in vivo administration of these agents did not alter the transglutaminase activity in rat hepatic tissue. The data demonstrate that sulfonylureas potentiate the responsiveness of the target tissues for insulin. Thus, these hypoglycemic agents probably act by correcting some of the cellular lesions associated with the insulin resistance in type II diabetes mellitus.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6376028&dopt=Abstract
Biochim Biophys Acta. 1984 Dec 6;796(3):328-35.
Effects of starvation and different culture conditions on the phospholipid content of isolated pancreatic islets.
Hallberg A.
A colorimetric method for the determination of lipid phosphorus in the nanomolar range was used to determine the total phospholipid content of isolated pancreatic islets. Freshly isolated islets of lean C57BL/6J mice contained significantly more phospholipids expressed per micrograms DNA as compared to C57BL/6J (ob/ob) mouse or Wistar rat islets. Starvation for 48 h (Wistar rats) or 60 h (NMRI mice) did not affect the islet phospholipid content. Phosphatidylcholine was the most abundant phospholipid class of NMRI mouse islets, followed by phosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and lysophosphatidylcholine. When islets of NMRI mice were maintained for 5-7 days in tissue culture, the phospholipid content remained unchanged as compared to that of freshly isolated islets despite a considerable loss of the insulin stores. The islet phospholipid content was significantly increased when the glucose concentration of the culture medium was elevated from 3 to 28 mM. Leucine (10 mM) added to a low-glucose medium failed to increase the islet phospholipid content. Addition of glipizide (2 microM) to the culture medium decreased the islet insulin content significantly but failed to affect the total islet phospholipid content. Culture in a Ca2+-free medium containing 28 mM glucose increased the islet insulin content but, again, the phospholipid content remained unaffected. These data show that changes of the total phospholipid content of pancreatic islets are unrelated to the islet insulin content and presumably also to the content of secretory granules. Alterations of the islet content of phospholipids may rather reflect changes of the amount of endoplasmic reticulum of the islet cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6391554&dopt=Abstract
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