期刊
PEPTIDES
卷 100, 期 -, 页码 165-172出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2017.12.020
关键词
Dipeptidyl-peptidase-4 (DPP-4); High fat fed; Type 2 diabetes; Islet; Insulin resistance
资金
- Department of Education and Learning, Northern Ireland
- Ulster University Strategic Funding
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < .01). Tissue distribution patterns in lean and HFF mice demonstrated highest levels of DPP-4 activity in lung (20-26 mu mol/min/mg protein) and small intestine (13-14 mu mol/min/mg protein), and lowest activity in the spleen (3.8 mu mol/min/mg protein). Modulation of DPP-4 activity by high fat feeding was observed in several tissues with increases in the lung (p < .05), liver (p < .05), kidney (p < .05) and pancreas (p < .05). With a high fat diet, DPP-4 gene expression was upregulated in the liver (p < .001) and downregulated in the pancreas (p < 0.001) and small intestine (p < .001). Immunohistochemical analysis revealed increased DPP-4 immunostaining localised primarily in the pancreatic islets of HFF mice (p < .01) with no change in islet GLP-1 expression. Treatment of HFF mice with metformin for 21-days resulted in inhibition of circulating DPP-4 activity (p < .05), decreased blood glucose (p < .05) and increased GLP-1 gene expression (p < .001). These data indicate that DPP-4 is modulated in a tissue specific manner and is dependent on physiological conditions such as hyperglycaemia and insulin resistance, suggesting a significant role in disorders such as diabetes.
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