Glucose intolerance and decreased early insulin response in mice with severe hypertriglyceridemia.
Hypertriglyceridemia (HTG) is one of the key features of dyslipidemia in type 2 diabetes, caused by the overproduction and/or decreased clearance of triglyceride (TG)-rich lipoproteins, and significantly promotes the development of cardiovascular diseases in diabetes. However, the effect of severe HTG on glucose metabolism has not previously been determined. Lipoprotein lipase (LPL) deficiency results in severe HTG in humans. By using LPL-deficient mice with severe HTG, we assessed the impact of severe HTG on insulin secretion and glucose tolerance in the present study. While young LPL-deficient mice (4 months of age) showed higher fasting blood glucose (7.42 +/- 0.84 versus 4.8 +/- 0.80 mmol/L, P < 0.01) and lower insulin concentrations (0.16 +/- 0.03 versus 0.48 +/- 0.14 ng/mL, P < 0.05), old mice (12 months of age) had higher insulin (1.70 +/- 0.35 versus 0.77 +/- 0.04 ng/mL, P < 0.05) but normal fasting blood glucose concentrations. Both young and old mice had elevated free fatty acid (FFA) concentrations and exhibited decreased early insulin response; however, only old mice showed impaired glucose tolerance, as compared with wild-type mice of a similar age. Morphological assessment showed enlarged islets in old LPL-deficient mice. These findings suggest that different tests for glucose homeostasis may be needed for patients with LPL deficiency and severe HTG, even though their glucose concentrations are normal at initial screening.
Ding
Yi-Lei
YL
Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Wang
Yu-Hui
YH
Huang
Wei
W
Liu
George
G
Ross
Colin
C
Hayden
Michael R
MR
Yang
Jin-Kui
JK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000235:genetics / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010179:Pancreas / Q000473:pathology
D001786:Blood Glucose; D007328:Insulin; D008071:Lipoprotein Lipase