Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs.
OBJECTIVE
Diabetes is a serious health problem. It has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs.


METHODS
Forty nondiabetic beagle dogs were randomly divided into 4 groups. Group 1 received daily intramuscular injections of vehicle, whereas the other 3 groups received daily INGAP injections of 0.5, 1.5, or 10 mg/kg. After 30 days, pancreatic tissues were collected, and RNA and histological sections were analyzed.


RESULTS
In dogs treated with 1.5 mg/kg INGAP, there was a significant (P < 0.001) increase in the percentage of insulin-positive cells (P < 0.001) and insulin gene expression. There was a trend to increased insulin-positive cells and gene expression with treatments of 0.5 and 10 mg/kg peptide. Protein gene product 9.5-positive cells were increased with treatment.


CONCLUSIONS
These results indicate that INGAP stimulates cells in the pancreatic duct epithelium of healthy dogs (putative islet progenitor cells) to develop along a neuroendocrine pathway and form new islets in response to INGAP peptide. The INGAP might be an effective therapy for diabetes.
Pittenger
Gary L
GL
Strelitz Diabetes Institutes, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23510, USA. pittengl@evms.edu
Taylor-Fishwick
David A
DA
Johns
Robert H
RH
Burcus
Niculina
N
Kosuri
Srivenkat
S
Vinik
Aaron I
AI
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics; D008297:Male; D008647:Mesocricetus; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins