beta-cell function in obesity: effects of weight loss.
In nondiabetic subjects, obesity is associated with a modest expansion of beta-cell mass, possibly amounting-according to the best available estimates-to 10-30% for each 10 kg of weight excess. Whether age of onset and duration of obesity, recent changes in body weight, and body fat distribution have any effect on beta-cell mass in humans is unknown. Both fasting insulin secretion and the total insulin response to oral glucose have the following characteristics: 1) they increase with BMI in an approximately linear fashion, 2) both fat-free and fat mass are significant positive correlates, and 3) BMI exerts a positive effect separate from that of insulin resistance (i.e., obesity may be a state of primary insulin hypersecretion). The mechanisms are currently unknown, though chronic small increments in plasma glucose may play a role. In contrast, dynamic properties of beta-cell function, such as glucose sensitivity (i.e., dose-response function), rate sensitivity, and potentiation, do not appear to be substantially altered by the presence of obesity, body fat distribution, or insulin resistance as long as glucose tolerance is maintained. Weight loss, by diet or restrictive bariatric surgery, is associated with consensual decrements in insulin resistance and insulin hypersecretion. The latter, however, seems to be more persistent, suggesting that the postobese state may reproduce the primary insulin hypersecretion of the obese state. Malabsorptive bariatric surgery, in contrast, normalizes insulin sensitivity and abolishes insulin hypersecretion even before achievement of ideal body weight. Lipid-triggered messages from the gastrointestinal tract to the insulin target tissues and endocrine pancreas are the subject of intense investigation.
Ferrannini
Ele
E
Department of Internal Medicine, Via Savi, 8, 56126 Pisa, Italy. ferranni@ifc.cnr.it
Camastra
Stefania
S
Gastaldelli
Amalia
A
Maria Sironi
Anna
A
Natali
Andrea
A
Muscelli
Elza
E
Mingrone
Geltrude
G
Mari
Andrea
A
D000818:Animals; D015992:Body Mass Index; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D009929:Organ Size; D015431:Weight Loss
D007328:Insulin