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Life Sci. 2004 Feb 27;74(15):1877-88.
Combination of metformin and thiazolidindiones restore insulin signalling in insulin-resistant cultured myotubes.

Kumar N, Kaul CL, Ishrath A, Dey CS.

Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.

We examined the effect of combination of thiazolidinediones (TZDs) and metformin on insulin-resistant skeletal muscle cells. The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin. The glucose uptake was significantly high at the combination of lower concentration (12.5 microM of TZDs and 100 microM of metformin) as compared to the combination of higher concentration (50 microM of TZDs and 400 microM of metformin). Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14761669&dopt=Abstract [PubMed - in process]

yale.edu

A significant proportion of women with polycystic ovary syndrome (PCOS) suffer from insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide a rationale for therapies focused on treatments of insulin resistance. Metformin is the most extensively studied insulin-sensitizing agent for the treatment of women with PCOS. Use of metformin leads to a decrease in serum insulin and androgen levels, as well as an improvement in ovulatory function. Other insulin-sensitizing agents studied in women with PCOS include troglitazone, rosiglitazone, pioglitazone, and D-chiro-inositol.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14764283&dopt=Abstract [PubMed - in process]




Metabolism. 2004 Feb;53(2):159-64.
Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus.

Abbasi F, Chu JW, McLaughlin T, Lamendola C, Leary ET, Reaven GM.

Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

In light of the conflicting results of the recent United Kingdom Prospective Study (UKPDS), where diabetic patients on metformin monotherapy had lower all-cause mortality and the addition of metformin in sulfonylurea-treated patients was associated with an increased risk of diabetes-related death, we sought to compare the effects on cardiovascular disease (CVD) risk factors of metformin monotherapy with metformin treatment when added to a sulfonylurea compound in patients with type 2 diabetes. Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks. Measurements were made of (1) fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), lipid, remnant lipoprotein cholesterol (RLP-C) levels, and low-density lipoprotein (LDL) particle size; (2) daylong plasma glucose, insulin, free fatty acid (FFA), triglyceride (TG), and RLP-C concentrations; and (3) fasting levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin). Fasting plasma glucose concentrations decreased to a similar degree after treatment with metformin in both the metformin monotherapy group (12.45 +/- 0.48 v 9.46 +/- 0.47 mmol/L, P <.001) and the combined SU and metformin therapy group (14.09 +/- 0.51 v 10.57 +/- 0.85 mmol/L, P =.001). Fasting plasma lipid concentrations and LDL particle size did not significantly change in either treatment group, whereas fasting RLP-C concentrations were significantly lower in the metformin monotherapy group (0.43 +/- 0.09 v 0.34 +/- 0.07 mmol/L, P =.02). Daylong concentrations of plasma glucose, FFA, TG, and RLP-C were lower to a similar degree in both treatment groups, whereas daylong plasma insulin concentrations were unchanged. Fasting plasma sVCAM-1 levels were significantly lower in both the metformin monotherapy group (484 +/- 19 v 446 +/- 18 ng/mL, P =.02) and the combined SU and metformin therapy group (496 +/- 29 v 456 +/- 31 ng/mL, P =.05), whereas fasting plasma sICAM-1 and sE-selectin levels were essentially unchanged. Administration of metformin, either as monotherapy or in combination with a sulfonylurea drug, improved glycemic control and led to a decrease in several CVD risk factors in patients with type 2 diabetes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14767866&dopt=Abstract [PubMed - in process]





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