Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats.

Abstract

We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0 microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.

• Authors: Moon K Song, In K Hwang, Mark J Rosenthal, Diane M Harris, Dean T Yamaguchi, Ian Yip, Vay Liang W Go
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 228 Issue 11 Pg. 1338-45 (Dec 2003) ISSN: 1535-3702 [Print] England
• PMID: 14681549 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Peptides, Cyclic
• Piperazines
• Glucose
• Zinc
• histidyl-proline diketopiperazine

Topics

• Aging (blood)
• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, genetics)
• Drinking (drug effects)
• Female
• Glucose (metabolism)
• Hypoglycemic Agents (administration & dosage, pharmacology)
• In Vitro Techniques
• Insulin (blood)
• Male
• Muscles (drug effects, metabolism)
• Peptides, Cyclic (administration & dosage, pharmacology)
• Piperazines (administration & dosage, pharmacology)
• Rats
• Rats, Inbred Strains
• Rats, Sprague-Dawley
• Rats, Wistar
• Zinc (administration & dosage, pharmacology)