Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model.
Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a diabetic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin-serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.
CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay F-91405, France.
Ioannis
I
Papazoglou
Flavien
F
Berthou
Nicolas
N
Vicaire
Claude
C
Rouch
Eirini M
EM
Markaki
Danielle
D
Bailbe
Bernard
B
Portha
Mohammed
M
Taouis
Kyriaki
K
Gerozissis
D000818:Animals; D001786:Blood Glucose; D045744:Cell Line, Tumor; D020372:Dexfenfluramine / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating; D006801:Humans; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D020738:Leptin / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D019518:Postprandial Period; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk; D011972:Receptor, Insulin / Q000378:metabolism; D012701:Serotonin / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D020372:Dexfenfluramine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt