Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice.
Am J Physiol Endocrinol Metab
; 302(8): E924-31, 2012 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-22275759
ABSTRACT
Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic ß-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 µg·kg⻹·day⻹), amylin (A; 100 µg·kg⻹·day⻹), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Fármacos Antiobesidad
/
Leptina
/
Diabetes Mellitus Tipo 2
/
Polipéptido Amiloide de los Islotes Pancreáticos
/
Hipoglucemiantes
/
Obesidad
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón