Weaning stage hyperglycemia induces glucose-insensitivity in arcuate POMC neurons and hyperphagia in type 2 diabetic GK rats. (April 2018)

• Record Type: Journal Article
• Authors: Ando, A.; Gantulga, D.; Nakata, M.; Maekawa, F.; Dezaki, K.; Ishibashi, S.; Yada, T.
• Is Part Of: Neuropeptides. Volume 68(2018)
• Page Start: 49
• Page End: 56
• Publication Date: 2018-04
• Subjects: ARC arcuate nucleus -- GK rat Goto-Kakizaki rat -- POMC pro-opiomelanocortin -- NPY Neuropeptide Y; Hyperglycemia -- Hyperphagia -- Glucose sensing -- POMC -- Weaning -- GK rat -- Type 2 diabetes; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2018.02.001
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstracts: Hyperphagia triggers and accelerates diabetes, and prevents proper dietary control of glycemia. Inversely, the impact of hyperglycemia on hyperphagia and possible mechanistic cause common for these two metabolic disorders in type 2 diabetes are less defined. The present study examined the precise developmental process of hyperglycemia and hyperphagia and explored the alterations in the hypothalamic arcuate nucleus (ARC), the primary feeding and metabolic center, in Goto-Kakizaki (GK) rats with type 2 diabetes and nearly normal body weight. At mid 3 to 4 weeks of age, GK rats first exhibited hyperglycemia, and then hyperphagia and reduced mRNA expressions for anorexigenic pro-opiomelanocortin (POMC) and glucokinase in ARC. Furthermore, [Ca 2+ ]i responses to high glucose in ARC POMC neurons were impaired in GK rats at 4 weeks. Treating GK rats from early 3 to mid 6 weeks of age with an anti-diabetic medicine miglitol not only suppressed hyperglycemia but ameliorated hyperphagia and restored POMC mRNA expression in ARC. These results suggest that the early hyperglycemia occurring in weaning period may lead to impaired glucose sensing and neuronal activity of POMC neurons, and thereby induce hyperphagia in GK rats. Correction of hyperglycemia in the early period may prevent and/or ameliorate the progression of hyperphagia in type 2 diabetes. Highlights: Goto-Kakizaki (GK) rats at weaning 4 weeks develop hyperglycemia and hyperphagia. Reduced POMC, glucokinase and glucose-induced [Ca2+]i rises in arcuate neurons. Anti-diabetic miglitol ameliorates hyperglycemia and hyperphagia and restores POMC. Early hyperglycemia induces POMC neuron dysfunction and hyperphagia in GK rats. Correcting hyperglycemia early may decelerate POMC reduction/hyperphagia in T2DM.