Anti-hyperglycemic, antioxidant and anti-inflammatory effects of VIP and a VPAC1 agonist on streptozotocin-induced diabetic mice.
Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide with potent anti-inflammatory properties, and its receptor, VPAC1, mediates most of the anti-inflammatory effects of VIP. Diabetes mellitus is characterized by increased oxidation and inflammation due to persistent hyperglycemia. This research was performed to investigate the effects of VIP and a VPAC1 agonist on streptozotocin (STZ)-induced type 1 diabetic mice. Intraperitoneal injection of VIP and VPAC1 agonist (50nmol/kg/day in saline) over a 28-day period (1) decreased food intake, (2) increased body weight, (3) improved visceral index, (4) increased the fasting plasma insulin levels, (5) decreased the fasting plasma glucose, (6) improved the glucose tolerance, (7) decreased pancreas H(2)O(2) and malondialdehyde (MDA) and (8) increased total antioxidant activity (T-AOC) in the liver, spleen and pancreas. The results of histopathological and immunohistochemical analysis showed that VIP and the VPAC1 agonist improved the structure and cellularity of islets and ameliorated the insulin-secreting activity of islets. Additionally, administration of VIP or the VPAC1 agonist not only significantly decreased the plasma TNFα and CRP and promoted IL-10 in diabetic mice but also blocked the increased NF-κB activity of pancreatic tissue in diabetic mice. Furthermore, the VPAC1 agonist displayed stronger effects than VIP. These results show that both VIP and VPAC1 agonist ameliorated STZ-induced diabetes and protected mice against oxidative stress and inflammation associated diabetes, with VPAC1 being the receptor most responsible for these positive effects in diabetic mice.
Bio-engineering Institute of Jinan University, Jinan University, Guangzhou 510632, China. rongjie yu1123@163.com
Rongjie
R
Yu
Huahua
H
Zhang
Lin
L
Huang
Xiaofei
X
Liu
Jiansu
J
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004435:Eating / Q000187:drug effects; D005951:Glucose Tolerance Test; D006861:Hydrogen Peroxide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000819:agonists*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D016328:NF-kappa B; D010446:Peptide Fragments; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014409:Tumor Necrosis Factor-alpha; C409214:vasoactive intestinal peptide (1-7)-GRF (8-27), Lys(15)-Arg(16)-Leu(27)-; D016753:Interleukin-10; D014660:Vasoactive Intestinal Peptide; D008315:Malondialdehyde; D002097:C-Reactive Protein; D006861:Hydrogen Peroxide