title: Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects.
abstract: Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject for a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the end of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5 %, 17 %), intermediate-dose (6 %, 25 %) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.
authors.affiliation: The Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, College of Medicine, Tainan, Taiwan.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Ou
authors.forename: J-T
authors.initials: JT
authors.lastname: Cheng
authors.forename: E H
authors.initials: EH
authors.lastname: Yu
authors.forename: T-J
authors.initials: TJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D001615:beta-Endorphin / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D008055:Lipids; D001615:beta-Endorphin; D002097:C-Reactive Protein; D008687:Metformin