Pancreas · 2007
Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs.
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Pittenger Gary L, Taylor-Fishwick David A, Johns Robert H, Burcus Niculina, Kosuri Srivenkat, Vinik Aaron I
Аннотация
OBJECTIVES: 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.
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.
Предметные рубрики MeSH
AnimalsAntigens, NeoplasmBiomarkers, TumorCell DivisionCricetinaeDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2DogsFemaleFluorescent Antibody TechniqueInjections, IntramuscularInjections, IntravenousIslets of LangerhansLectins, C-TypeMaleMesocricetusPancreatitis-Associated ProteinsRNA, MessengerRecombinant Fusion ProteinsRegeneration