کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8347491 | 1541679 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tissue expression of DPP-IV in obesity-diabetes and modulatory effects on peptide regulation of insulin secretion
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
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 (pâ¯<â¯.01), were hyperglycaemic (pâ¯<â¯.01) and hyperinsulinaemic (pâ¯<â¯.05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (pâ¯<â¯.01). Tissue distribution patterns in lean and HFF mice demonstrated highest levels of DPP-4 activity in lung (20-26â¯Î¼mol/min/mg protein) and small intestine (13-14â¯Î¼mol/min/mg protein), and lowest activity in the spleen (3.8â¯Î¼mol/min/mg protein). Modulation of DPP-4 activity by high fat feeding was observed in several tissues with increases in the lung (pâ¯<â¯.05), liver (pâ¯<â¯.05), kidney (pâ¯<â¯.05) and pancreas (pâ¯<â¯.05). With a high fat diet, DPP-4 gene expression was upregulated in the liver (pâ¯<â¯.001) and downregulated in the pancreas (pâ¯<â¯0.001) and small intestine (pâ¯<â¯.001). Immunohistochemical analysis revealed increased DPP-4 immunostaining localised primarily in the pancreatic islets of HFF mice (pâ¯<â¯.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 (pâ¯<â¯.05), decreased blood glucose (pâ¯<â¯.05) and increased GLP-1 gene expression (pâ¯<â¯.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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 100, February 2018, Pages 165-172
Journal: Peptides - Volume 100, February 2018, Pages 165-172
نویسندگان
Aine M. McKillop, Claire L. Stevenson, Brian M. Moran, Yasser H.A. Abdel-Wahab, Peter R. Flatt,