title: Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients.
abstract: Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinaemic-euglycaemic clamp technique with infusion of 3-[3H]-glucose in eight obese NIDDM patients and in eight obese non-diabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu: 180.5 +/- 25.8 vs. 225.3 +/- 39.9 mU/l, P < 0.05), but not in non-diabetics (140 +/- 15.3 vs. 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and non-diabetics. When non-diabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P < 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production (HGP) is completely suppressed (HGP0) (P < 0.01). In conclusion, fluoxetine improves peripheral and hepatic insulin action in obese insulin-resistant subjects irrespective of its weight lowering effect.
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital, Leiden, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Potter van Loon
authors.forename: J K
authors.initials: JK
authors.lastname: Radder
authors.forename: M
authors.initials: M
authors.lastname: Frölich
authors.forename: H M
authors.initials: HM
authors.lastname: Krans
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: A E
authors.initials: AE
authors.lastname: Meinders
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005473:Fluoxetine; D005947:Glucose