1. Weaning stage hyperglycemia induces glucose-insensitivity in arcuate POMC neurons and hyperphagia in type 2 diabetic GK rats
- Author
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Shun Ishibashi, Fumihiko Maekawa, Masanori Nakata, Katsuya Dezaki, Akihiko Ando, Darambazar Gantulga, and Toshihiko Yada
- Subjects
Blood Glucose ,Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Pro-Opiomelanocortin ,Weaning ,Type 2 diabetes ,Hyperphagia ,Eating ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Endocrinology ,Arcuate nucleus ,Diabetes mellitus ,Internal medicine ,medicine ,Animals ,Premovement neuronal activity ,Rats, Wistar ,Neurons ,Arc (protein) ,Endocrine and Autonomic Systems ,business.industry ,Glucokinase ,Miglitol ,digestive, oral, and skin physiology ,Arcuate Nucleus of Hypothalamus ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,Glucose ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Neurology ,Hyperglycemia ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
s 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, [Ca2+]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.
- Published
- 2018