title: Estimates of hepatic glyceroneogenesis in type 2 diabetes mellitus in humans.
abstract: Glyceroneogenesis, that is, formation of triglyceride-glycerol from pyruvate, is a critical component of triglyceride fatty acid cycling in vivo. The quantitative contribution of glyceroneogenesis to triglyceride-glycerol and its hormonal regulation have not been examined in humans. We have quantified the contribution of pyruvate to very low-density lipoprotein (VLDL) triglycerides in subjects with type 2 diabetes mellitus using the deuterium labeling of body water technique. Subjects with type 2 diabetes mellitus were studied before and after a 6-month behavioral intervention therapy, during fasting and during a hyperinsulinemic normoglycemic clamp. Response to glucagon infusion was examined in 5 healthy subjects after an overnight fast. Glyceroneogenesis contributed approximately 54% to VLDL triglyceride-glycerol in type 2 diabetes mellitus as compared with approximately 12% contribution of plasma glucose. There was no effect of insulin plus glucose during hyperinsulinemic clamp on glyceroneogenesis even after clinical interventions, when insulin sensitivity had improved. In healthy subjects, the contribution of triosephosphates to plasma VLDL triglycerides was approximately 45%. Glyceroneogenesis, in contrast to glycolysis, is the predominant source of triglyceride-glycerol carbon for VLDL triglycerides in subjects with type 2 diabetes mellitus. The contribution of glyceroneogenesis to triglyceride-glycerol is not affected by short (4 hours) infusion of insulin in type 2 diabetes mellitus.
authors.affiliation: Schwartz Center for Nutrition and Metabolism, MetroHealth Center, Cleveland, OH 44109, USA. sck@case.edu
authors.forename: Satish C
authors.initials: SC
authors.lastname: Kalhan
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: McCullough
authors.forename: Richard W
authors.initials: RW
authors.lastname: Hanson
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019289:Pyruvic Acid / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis* / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D019289:Pyruvic Acid; D005947:Glucose; D005990:Glycerol