کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3276126 1208529 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The insulin-signaling pathway of the pancreatic islet is impaired in adult mice offspring of mothers fed a high-fat diet
ترجمه فارسی عنوان
مسیر انسولین سیگنالینگ جزیره پانکراس در موشهای بزرگسال بالغ از مادران تغذیه با رژیم غذایی با چربی بالا
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی غدد درون ریز، دیابت و متابولیسم
چکیده انگلیسی


• Maternal high-fat diet (MHF) leads to remodeling altering the natural disposition of alpha / beta cells in pancreatic islet of male offspring in adulthood.
• ​MHF causes alpha / beta cell hyperplasia as an adaptive response to hyperglycemia in pancreatic islet of male offspring in adulthood.
• ​MHF impairs insulin-signaling pathway in pancreatic islet of male offspring in adulthood.

ObjectiveMothers fed a high-fat (HF) diet can cause different adverse alterations in their offspring. The study aimed to verify the pancreatic islet structure and insulin-signaling pathway in adulthood of offspring of mothers fed a HF diet during the pregnancy.MethodsFemale mice (mothers) were randomly assigned to receive either standard chow (Mo-SC) or a HF diet (Mo-HF) ad libitum. After 2 mo on the experimental diets, 3-mo-old female mice were mated with male C57 BL/6 mice that were fed a SC diet. The male offspring was evaluated at 6 mo old.ResultsAt 6 mo of age, Mo-HF offspring had an increment in body mass and adiposity, hypercholesterolemia, and hypertriacylglycerolemia, higher levels of insulin, and leptin with a concomitant decrease in adiponectin levels. In the islet, we observed an alteration in the structure characterized by the migration of some alpha cells from the edge to the core of the islet in association with an increase in the masses of the islet, beta cell, and alpha cell, featuring a pancreatic islet remodeling. Additionally, the Mo-HF offspring demonstrated a decrease in IRS1, PI3 k p-Akt, Pd-1, and Glut2 protein expressions compared to Mo-SC offspring. However, an increase was observed in FOXO1 and insulin protein expressions in Mo-HF offspring compared to Mo-SC offspring.ConclusionThe present study demonstrated that a maternal HF diet is responsible for remodeling the islet structure coupled with an adverse carbohydrate metabolism and impairment of the insulin-signaling pathway in adult male mice offspring.

Maternal high-fat diet alters insulin-signaling in the pancreas (Akt-PI3 k pathway) of offspring in adulthood, resulting in a framework of beta cell dysfunction. The insulin-signaling activation needs an insulin receptor substrate (IRS1) in beta cells, which was decreased in the Mo-HF offspring, featuring a downregulation of the Akt-PI3 k signaling. With the impairment of the pathway, FOXO1 is overexpressed, resulting in Pdx-1 inhibition impairing the regulation of genes, such as Glut2. Adult offspring from mother fed HF diet during pregnancy showed beta cell dysfunction with compensatory hypersecretion of insulin and hyperglycemia. Up-arrows (↑) indicate an increase in protein expression and down-arrows (↓) indicate a decrease in protein expression. Forkhead box protein O1 (FOXO1); glucose transporter 2 (GLUT2); insulin receptor substrate 1 (IRS1); phosphatidylinositide 3-kinase (PI3 K); pyruvate dehydrogenase kinase (PDK1); protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase; pancreatic and duodenal homeobox 1(Pdx1).Figure optionsDownload high-quality image (259 K)Download as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nutrition - Volume 32, Issue 10, October 2016, Pages 1138–1143
نویسندگان
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