Effects of subchronic treatment with the long-acting glucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in streptozotocin-induced diabetes.
OBJECTIVE
N-AcGIP is a potent and dipeptidylpeptidase IV-resistant analogue of glucose-dependent insulinotropic polypeptide with significantly improved antidiabetic actions in type 2 diabetes. The present study investigated the effects of subchronic treatment with N-AcGIP on glucose homeostasis in a type 1 model, namely, streptozotocin (STZ)-induced diabetic mice.


METHODS
Swiss TO mice given a single intraperitoneal injection of STZ (150 mg/kg body weight) received once-daily injection of N-AcGIP (25 nmol/kg body weight) or saline for 20 days and effects on metabolic parameters and islet architecture assessed.


RESULTS
Daily injection of N-AcGIP for 20 days did not significantly alter the characteristic STZ-induced changes of pancreatic insulin content, body weight, food intake, glucose, and glycated hemoglobin levels. Glucose tolerance and insulin sensitivity were also unchanged by N-AcGIP treatment. Circulating insulin was undetectable, and the number of intact islets and insulin expression was greatly reduced in both groups. Some proliferative activity was identified by 5-bromo-2-deoxyuridine staining in the pancreas, but this and expression of glucagon and somatostatin were similar in the 2 groups.


CONCLUSIONS
These data indicate that subchronic treatment with the long-acting glucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, does not have beneficial effects in insulin-deficient STZ-diabetic mice. This supports the primary antidiabetic action of this analogue in type 2 diabetes as stimulation of beta-cell function and insulin secretion.
Gault
Victor A
VA
Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK. va.gault@ulster.ac.uk
McClean
Paula L
PL
Irwin
Nigel
N
Power
Gavin J
GJ
McCluskey
Janie T
JT
Flatt
Peter R
PR
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D013004:Somatostatin / Q000378:metabolism
D001786:Blood Glucose; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007328:Insulin; D013004:Somatostatin; C512327:N-AcGIP(LysPAL37)