High passage MIN6 cells have impaired insulin secretion with impaired glucose and lipid oxidation.
Type 2 diabetes is a metabolic disorder characterized by the inability of beta-cells to secrete enough insulin to maintain glucose homeostasis. MIN6 cells secrete insulin in response to glucose and other secretagogues, but high passage (HP) MIN6 cells lose their ability to secrete insulin in response to glucose. We hypothesized that metabolism of glucose and lipids were defective in HP MIN6 cells causing impaired glucose stimulated insulin secretion (GSIS). HP MIN6 cells had no first phase and impaired second phase GSIS indicative of global functional impairment. This was coupled with a markedly reduced ATP content at basal and glucose stimulated states. Glucose uptake and oxidation were higher at basal glucose but ATP content failed to increase with glucose. HP MIN6 cells had decreased basal lipid oxidation. This was accompanied by reduced expressions of Glut1, Gck, Pfk, Srebp1c, Ucp2, Sirt3, Nampt. MIN6 cells represent an important model of beta cells which, as passage numbers increased lost first phase but retained partial second phase GSIS, similar to patients early in type 2 diabetes onset. We believe a number of gene expression changes occurred to produce this defect, with emphasis on Sirt3 and Nampt, two genes that have been implicated in maintenance of glucose homeostasis.
Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Kim
K
Cheng
Viviane
V
Delghingaro-Augusto
Christopher J
CJ
Nolan
Nigel
N
Turner
Nicole
N
Hallahan
Sofianos
S
Andrikopoulos
Jenny E
JE
Gunton
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D042541:Intracellular Space / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008954:Models, Biological; D010084:Oxidation-Reduction
D007328:Insulin; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose