Glucose intolerance in young TallyHo mice is induced by leptin-mediated inhibition of insulin secretion.
The pathophysiology of TallyHo mouse, a recently established animal model for type 2 diabetes mellitus, was analyzed at prediabetic state to examine the inherent defects which contribute to the development of diabetes. At 4 weeks of age, the TallyHo mice already revealed glucose intolerance while their peripheral tissues exhibited normal insulin sensitivity. On the other hand, decreased plasma insulin concentration was observed with little differences in pancreatic insulin contents, indicating the impaired insulin secretion. Such defect, however, was not found in the isolated islets, which suggests a role of endocrine factor in impaired insulin secretion of TallyHo mice. Treatment of leptin inhibited the glucose-stimulated insulin secretion from the isolated islets of TallyHo mice, while in vivo administration of anti-leptin antibody lowered plasma glucose concentration with increased insulin level in TallyHo mice. Expression of glucokinase mRNA was decreased both in whole pancreas and leptin treated islets of TallyHo mice compared with whole pancreas in C57BL/6 mice and untreated islets of TallyHo mice, respectively. These results suggest that elevated plasma leptin can, through the inhibition of insulin secretion, induce glucose intolerance in TallyHo mice.
Sung
Yoon-Young
YY
Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yusong, Daejon 305-345, Republic of Korea.
Lee
Young-Sil
YS
Jung
Won Hoon
WH
Kim
Hee-Youn
HY
Cheon
Hyae Gyeong
HG
Yang
Sung-Don
SD
Rhee
Sang Dal
SD
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D005941:Glucokinase / Q000096:biosynthesis; D018149:Glucose Intolerance / Q000209:etiology*; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000378:metabolism; D011236:Prediabetic State / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D054411:Receptors, Leptin
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D005941:Glucokinase