IGF-I overexpression does not promote compensatory islet cell growth in diet-induced obesity.
Although IGF-I was known to stimulate the growth of pancreatic islet cells from early in vitro experiments and in vivo reports on rodents, recent gene targeting experiments have indicated that IGF-I and its receptor do not play a major role in normal islet cell growth. In our previous reports, liver- or pancreatic-specific IGF-I deficiency caused no decrease in β-cell mass; a general and β-cell-enriched IGF-I overexpression caused no change in normal islet cell growth. On the other hand, increased metabolic demands (such as in obesity and insulin resistance) result in β-cell compensation in cell number and insulin secretion. In order to test whether IGF-I could promote islet cell growth and facilitate islet compensation due to obesity-induced insulin resistance, we have challenged MT-IGF mice to a high-fat diet. After 28 weeks, both MT-IGF mice and wild-type littermates gained comparable 40-57% of body weight, with similar increases in fat masses; all mice maintained a normal sensitivity to insulin and did not become severely hyperglycemic. Nevertheless, compared to wild-type littermates, the equally obese MT-IGF mice maintained improved glucose tolerance and a diminished insulin level; similar to when fed a normal chow diet. More importantly, under IGF-I overexpression, there was no further increase in β-cell mass caused by obesity. Thus, IGF-I overexpression had no significant effect on weight gain and islet cell compensation in response to high-fat diet-induced obesity.
Robertson
Katie
K
Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Room H5-21, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada.
Dong
Jing
J
De Jesus
Kristine
K
Liu
Jun-Li
JL
D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D018149:Glucose Intolerance; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D013997:Time Factors
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D007334:Insulin-Like Growth Factor I