dorsomorphin and Hyperglycemia

Topics: Abietanes; AMP-Activated Protein Kinases; Blotting, Western; Cell Line; Cell Membrane; Cell Membrane Permeability; E1A-Associated p300 Protein; Electric Impedance; Fluorescein-5-isothiocyanate; Fluorescent Antibody Technique, Indirect; Glucose; Humans; Hyperglycemia; Immunosuppressive Agents; NF-kappa B p50 Subunit; Phosphorylation; Pyrazoles; Pyrimidines; Retinal Pigment Epithelium; Signal Transduction

Nesfatin-1 is recently reported as a satiety molecule to suppress food intake via the melanocortin signaling in hypothalamus when injected centrally and peripherally. Here we report that nesfatin-1 is also anti-hyperglycemic. It was found that the intravenous injection of nesfatin-1 significantly reduced blood glucose in hyperglycemic db/db mice. This anti-hyperglycemic effect of nesfatin-1 was time-, dose-, insulin-dependent and peripheral.

Topics: Anilides; Animals; Appetite Depressants; Blood Glucose; Calcium-Binding Proteins; DNA-Binding Proteins; Eating; Hyperglycemia; Hypolipidemic Agents; Insulin; Mice; Mice, Mutant Strains; Nerve Tissue Proteins; Nucleobindins; Peptide Hormones; Pyrazoles; Pyrimidines; Receptors, Leptin; Rosiglitazone; Thiazolidinediones

Macrophages (MPhis) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model.. The data demonstrate that peritoneal MPhis from diabetic (db/db) mice had reduced macropinocytosis when compared to MPhis from non-diabetic (db/+) mice. Additionally, MPhis cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MPhis cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-beta-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis.. Taken together, these findings indicate that MPhis from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MPhis and suggest that increasing AMPK activity in diabetic MPhis could improve innate immunity and decrease susceptibility to infection.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Cell Culture Techniques; Cell Line, Tumor; Diabetes Mellitus, Type 2; Disease Models, Animal; Energy Metabolism; Glucose; Hyperglycemia; Immunity; Leptin; Macrophage Activation; Macrophages, Peritoneal; Mice; Pinocytosis; Pyrazoles; Pyrimidines; Ribonucleosides