title: Combined hyperinsulinemia and hyperglycemia, but not hyperinsulinemia alone, suppress human skeletal muscle lipolytic activity in vivo.
abstract: Effects of circulating insulin and glucose concentrations on skeletal muscle and adipose tissue lipolytic activity were investigated in 10 type 1 diabetes patients with no endogenous insulin secretion. Microdialysis measurements of interstitial glycerol and determination of fractional glycerol release were carried out during standardized combinations of relative hypoinsulinemia/moderate hyperglycemia (11 mmol/liter), hyperinsulinemia/ normoglycemia (5 mmol/liter), and hyperinsulinemia/moderate hyperglycemia, respectively. Local tissue blood flow rates were measured with the (133)Xe clearance technique. In response to the change from hypo- to hyperinsulinemia, the fractional release of glycerol decreased from 159.6 +/- 17.8 to 85.1 +/- 13.7 micromol/liter (P < 0.0001) in adipose tissue, whereas it remained unchanged in skeletal muscle (44.6 +/- 6.4 vs. 36.0 +/- 7.4 micromol/liter; not significant). When hyperinsulinemia was combined with hyperglycemia, fractional glycerol release was further reduced in adipose tissue (64.5 +/- 12.2 micromol/liter; P < 0.05), and in this situation it was also markedly decreased in skeletal muscle (18.1 +/- 4.8 micromol/liter; P < 0.0001). Skeletal muscle blood flow was unaltered over the respective study periods. Adipose tissue blood flow decreased by 50% in response to hyperinsulinemia (P < 0.0005), but no further change was seen when hyperinsulinemia was combined with hyperglycemia. It is concluded that in patients with type 1 diabetes, insulin does not exert an antilipolytic effect in skeletal muscle during normoglycemia. However, in response to combined hyperinsulinemia and hyperglycemia, the lipolytic activity in skeletal muscle is restrained in a similar way as in adipose tissue. This may be explained by a glucose-mediated potentiation of the antilipolytic effectiveness of insulin.
authors.affiliation: Department of Medicine, M 63, Karolinska University Hospital-Huddinge, S-141 86 Stockholm, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Qvisth
authors.forename: Eva
authors.initials: E
authors.lastname: Hagström-Toft
authors.forename: Staffan
authors.initials: S
authors.lastname: Enoksson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.forename: Stefan
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Jan
authors.initials: J
authors.lastname: Bolinder
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D005990:Glycerol / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D012039:Regional Blood Flow
chemical_list: D008071:Lipoprotein Lipase; D005990:Glycerol