Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice
| Autor: | Takeshi Shimada, Yoshiko Morita, Norihito Shintani, Tatsuya Ojika, Masanori Nakata, Shuhei Tomimoto, Hitoshi Hashimoto, Kazuya Ikeda, Ken-ichi Hamagami, Yusuke Sakurai, Chie Ishida, Toshihiko Yada, Akemichi Baba |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Time Factors Adipose Tissue White Adipose tissue White adipose tissue Biology Fatty Acid-Binding Proteins Eating Islets of Langerhans Mice chemistry.chemical_compound Insulin resistance Internal medicine Adipocyte medicine Animals Homeostasis Insulin Glucose homeostasis Resistin RNA Messenger Triglycerides Mice Knockout Pharmacology Glucose tolerance test medicine.diagnostic_test lcsh:RM1-950 Body Weight Lipid metabolism Organ Size Glucose Tolerance Test medicine.disease Dietary Fats lcsh:Therapeutics. Pharmacology Endocrinology chemistry Pituitary Adenylate Cyclase-Activating Polypeptide Molecular Medicine Energy Metabolism hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Pharmacological Sciences, Vol 107, Iss 1, Pp 41-48 (2008) |
| ISSN: | 1347-8648 1347-8613 |
| Popis: | Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide implicated in several metabolic functions, including insulin secretion and sympathoadrenal activation. To clarify the roles of PACAP in maintenance of whole-body glucose and lipid homeostasis, the impact of the deletion of PACAP on glucose homeostasis, body weight, and adipose tissue mass was examined by comparing mice lacking the Adcyap1 gene encoding PACAP (Adcyap1−/−) with wild-type littermate controls. Adcyap1−/− mice showed significant hypoinsulinemia, although being normoglycemic, and lower body weight as well as reduced food intake. They also showed greatly reduced white adipose tissue mass, in which the mRNA expression of adipocyte fatty acid-binding protein (aP2), a marker of adipocyte differentiation, was decreased. Glucose and insulin tolerance tests revealed increased insulin sensitivity in Adcyap1−/− mice. In accordance with these observations, plasma levels of resistin, an adipocytokine implicated in insulin resistance, were decreased in Adcyap1−/− mice. After a high-fat dietary challenge for six weeks, Adcyap1−/− mice still showed lower body weights and increased insulin sensitivity. These results indicate the crucial roles of PACAP in energy metabolism, including lipid metabolism, and in the regulation of body weight, raising the possibility that the PACAP-signaling pathway that favors energy storage could be a therapeutic target for obesity. Keywords:: adipose tissue, body weight, insulin sensitivity, pituitary adenylate cyclase-activating polypeptide (PACAP), resistin |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|