scholarly journals Influence of a high-fat diet during chronic hyperglycemia on beta-cell function in pancreatic islet transplants to streptozotocin-diabetic rats

2001 ◽  
pp. 521-527 ◽  
Author(s):  
S Hiramatsu ◽  
V Grill
Keyword(s):  
Fatty Acids ◽  
Beta Cell ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Fat ◽  
Negative Effects ◽  
Low Fat ◽  
Low Fat Diet ◽  
Chronic Hyperglycemia

Chronically elevated non-esterified fatty acids (NEFAs) can exert negative effects on beta-cell function both in vitro and in vivo. Negative effects of fatty acids have been difficult to evaluate in overt diabetes because of the attendant hyperglycemia that gives rise to the confounding influence of 'glucotoxicity'. In this work, we tested for the effects of NEFAs in diabetes by (i) taking into account potential effects of prevailing levels of hyperglycemia, and (ii) focusing on lingering (and therefore possibly more serious) effects. A diabetic transplantation model was used in which two islet grafts with 200 and 20 rat islets respectively were transplanted under the kidney capsule of syngeneic recipients previously made diabetic by streptozotocin injection. Rats were then fed either a high-fat or a low-fat diet for 7 weeks, followed by 1 week of normal laboratory chow. During dietary intervention, food was consumed ad libitum in one protocol, but was restricted in the low-fat group in a second protocol (in order to match blood-glucose levels). A high-fat diet did not affect body weight. At the end of the protocols, graft-bearing kidneys were isolated and perfused. Insulin responses to 27.8 mM glucose in perfusion were uniformly absent, in keeping with previously documented effects of chronic hyperglycemia. In contrast, 10 mM arginine induced a marked increase in insulin secretion after a low-fat diet, an effect that was significantly reduced after a high-fat diet (109 +/- 39 vs 13 +/- 15 fmol/min (P < 0.05) and 95 +/- 18 vs 32 +/- 5 fmol/min (P < 0.05) in the 2 protocols respectively). Regardless of protocol, no effect of diet could be detected on graft contents of insulin or preproinsulin mRNA. Thus, under conditions in which influences of chronic hyperglycemia could be accounted for, a previous high-fat diet with elevated NEFAs inhibited arginine-induced insulin secretion; however, the results indicate that insulin biosynthesis and/or beta-cell mass were not affected.

scholarly journals Herring Milt and Herring Milt Protein Hydrolysate Reduce Weight Gain and Improve Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1699-1699
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Cell Function ◽  
Protein Hydrolysate ◽  
Oral Glucose ◽  
High Fat ◽  
Low Fat ◽  
Insulin Resistant ◽  
Low Fat Diet ◽  
Dietary Casein

Abstract Objectives The present study was designed to examine the effect of herring milt dry powder (HMDP) on glucose homeostasis and related metabolic phenotypes and compare its efficacy with herring milt protein hydrolysate (HMPH) in diet-induced obese and insulin resistant mice. Methods Male C57BL/6 J mice were pretreated with a high-fat diet for 7 weeks were divided into 3 groups where one group continued on the high-fat diet and used as the obese and insulin resistant control (HFC) and the other two groups were fed a modified HFC diet where 70% of casein was replaced with an equal percentage of protein derived from HMDP or HMPH. A group of mice fed a low-fat diet all the time was used as the normal or low-fat control (LFC). Body weight was obtained weekly and food intake was recorded daily. Semi-fating (4–6 hr) blood glucose was measured every other week using a glucometer using the blood from tail vein. Oral glucose tolerance was measured twice during weeks 5 and 9, respectively, and insulin tolerance was determined during week 7 of the treatment. At the end of the experiment, serum was obtained following overnight fasting for the measurement of fasting insulin, leptin, free fatty acids and lipids as well as other glucose metabolism-related biomarkers. Results During the 9-week treatment period, mice on the high-fat diet maintained significantly higher body weight and semi-fasting blood glucose levels and exhibited impaired oral glucose tolerance and insulin resistance relative to mice on the low-fat diet. At the end of the study, the analysis of fasting blood samples revealed that mice on the high-fat diet had increases in serum insulin, leptin, free fatty acids and cholesterol levels. Mice fed the high-fat diet also showed an increase in insulin resistance index and a decrease in β-cell function index. Compared to mice on the high-fat diet, the 70% replacement of dietary casein with an equal percentage of protein derived from HMDP or HMPH reversed or markedly improved these parameters, and HMDP and HMPH showed similar effects. Conclusions The results demonstrate that replacing dietary casein with the same amount of protein derived from either HMDP or HMPH prevents and improves high-fat-diet-induced obesity and insulin resistance. Funding Sources Atlantic Canada Opportunity Agency through the Atlantic Innovation Fund grant (no. 193,594) and National Research Council of Canada – NHP program.

scholarly journals AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet

2019 ◽  
Vol 240 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Niels L Mulder ◽  
Rick Havinga ◽  
Joost Kluiver ◽  
Albert K Groen ◽  
Janine K Kruit
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Gene Transfer ◽  
Beta Cell ◽  
Beta Cells ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
Beta Cell Proliferation ◽  
High Fat

MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo. To overexpress miR-132 specifically in beta cells, we employed adeno-associated virus (AAV8)-mediated gene transfer using the rat insulin promoter in a double-stranded, self-complementary AAV vector to overexpress miR-132. Treatment of mice with dsAAV8-RIP-mir132 increased miR-132 expression in beta cells without impacting expression of miR-212 or miR-375. Surprisingly, overexpression of miR-132 did not impact glucose homeostasis in chow-fed animals. Overexpression of miR-132 did improve insulin secretion and hence glucose homeostasis in high-fat diet-fed mice. Furthermore, miR-132 overexpression increased beta cell proliferation in mice fed a high-fat diet. In conclusion, our data show that AAV8-mediated gene transfer of miR-132 to beta cells improves beta cell function in mice in response to a high-fat diet. This suggests that increased miR-132 expression is beneficial for beta cell function during hyperglycemia and obesity.

Abstract 128: Short-Term, High-Saturated and Trans Fatty Acid Diet Increases Expression of Key Intestinal Genes Involved in Lipoprotein Metabolism in Healthy Males

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
André J Tremblay ◽  
Benoit Lamarche ◽  
Valerie Guay ◽  
Valery Lemelin ◽  
Patrick Couture
Keyword(s):  
Fatty Acids ◽  
Apolipoprotein B ◽  
High Fat Diet ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
High Fat ◽  
Low Fat ◽  
Short Term ◽  
Low Fat Diet ◽  
Key Genes

Dietary saturated fat (SFA) and trans fatty acids (TFA) have been linked to an increased risk of cardiovascular disease mainly by increasing plasma LDL-C levels. The modulation of cholesterol and fatty acids homeostasis by SFA and TFA is thought to be mediated by changes in expression of key intestinal genes involved in lipid and lipoprotein metabolism. However, the short-term impact of dietary fat intake on expression of these genes has not been fully investigated. To test whether short-term changes in SFA and TFA intake affects expression of key intestinal genes involved in lipid and lipoprotein metabolism, we conducted a randomized, double-blind, cross-over study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: 1) high-fat diet (37% energy from fat, 15% from SFA, 3.5% from TFA and 50% energy from carbohydrate) and 2) low-fat diet (25% energy from fat, 6% from SFA, 0% from TFA and 62% energy from carbohydrate) in random order, each separated by a two-week washout period. Fasting plasma lipid levels were determined and expression of key genes involved in lipid and lipoprotein metabolism was compared by real-time PCR quantification in duodenal biopsy specimens obtained in the fasted state after 3 days of feeding on each diet. Following the 3-day high-fat diet, plasma-C (+7.4%, P=0.02), LDL-C (+16.9%, P=0.005) and HDL-C (+9.3%, P=0.002) levels were significantly increased as compared to low-fat diet. Plasma triglycerides (-31.7%, P=0.001) and apolipoprotein B-48 (-39.6%, P=0.003) levels were significantly decreased after the high-fat diet relative to the low-fat diet. The high-fat diet also resulted in significant increases in intestinal mRNA expression levels of SREBP-2, HNF-4α, PPAR-α, PPAR-γ, NPC1L1, ABCG8, FABP-2, ACAC-α, SCD-1, ELOVL5, DGAT-2, apolipoprotein B, MTTP, SAR1β and LDL receptor. These findings suggest that short-term exposure to a high-SFA and TFA diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level.

PS2 - 7. MicroRNA-132 improves beta-cell function in high-fat diet fed mice

2013 ◽  
Vol 11 (4) ◽  
pp. 186-186
Author(s):  
Janine K. Kruit ◽  
Niels L. Mulder ◽  
Rick Havinga ◽  
Albert K. Groen
Keyword(s):  
Beta Cell ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Fat

scholarly journals Dietary Interventions for the Prevention of Type 2 Diabetes in High-Risk Groups: Current State of Evidence and Future Research Needs

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1245 ◽  
Author(s):  
Nicola Guess
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Minor Role ◽  
Intermittent Fasting ◽  
Low Fat ◽  
Low Fat Diet

A series of large-scale randomised controlled trials have demonstrated the effectiveness of lifestyle change in preventing type 2 diabetes in people with impaired glucose tolerance. Participants in these trials consumed a low-fat diet, lost a moderate amount of weight and/or increased their physical activity. Weight loss appears to be the primary driver of type 2 diabetes risk reduction, with individual dietary components playing a minor role. The effect of weight loss via other dietary approaches, such as low-carbohydrate diets, a Mediterranean dietary pattern, intermittent fasting or very-low-energy diets, on the incidence of type 2 diabetes has not been tested. These diets—as described here—could be equally, if not more effective in preventing type 2 diabetes than the tested low-fat diet, and if so, would increase choice for patients. There is also a need to understand the effect of foods and diets on beta-cell function, as the available evidence suggests moderate weight loss, as achieved in the diabetes prevention trials, improves insulin sensitivity but not beta-cell function. Finally, prediabetes is an umbrella term for different prediabetic states, each with distinct underlying pathophysiology. The limited data available question whether moderate weight loss is effective at preventing type 2 diabetes in each of the prediabetes subtypes.

scholarly journals Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice

2014 ◽  
Vol 95 (4) ◽  
pp. 296-308 ◽  
Author(s):  
Ricardo B. d. Oliveira ◽  
Carolina P. d. F. Carvalho ◽  
Carla C. Polo ◽  
Gabriel d. G. Dorighello ◽  
Antônio C. Boschero ◽  
...  
Keyword(s):  
Beta Cell ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
Ldl Receptor ◽  
High Fat ◽  
Ldl Receptor Knockout Mice

scholarly journals ZBED6 counteracts high-fat diet-induced glucose intolerance by maintaining beta cell area and reducing excess mitochondrial activation

Diabetologia ◽  
2021 ◽  
Author(s):  
Xuan Wang ◽  
Shady Younis ◽  
Jing Cen ◽  
Yun Wang ◽  
Camilla Krizhanovskii ◽  
...  
Keyword(s):  
Beta Cell ◽  
Glucose Intolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Area ◽  
High Fat ◽  
Beta Cell Area

Abstract Aims/hypothesis ZBED6 (zinc finger, BED-type containing 6) is known to regulate muscle mass by suppression of Igf2 gene transcription. In insulin-producing cell lines, ZBED6 maintains proliferative capacity at the expense of differentiation and beta cell function. The aim was to study the impact of Zbed6 knockout on beta cell function and glucose tolerance in C57BL/6 mice. Methods Beta cell area and proliferation were determined in Zbed6 knockout mice using immunohistochemical analysis. Muscle and fat distribution were assessed using micro-computed tomography. Islet gene expression was assessed by RNA sequencing. Effects of a high-fat diet were analysed by glucose tolerance and insulin tolerance tests. ZBED6 was overexpressed in EndoC-βH1 cells and human islet cells using an adenoviral vector. Beta cell cell-cycle analysis, insulin release and mitochondrial function were studied in vitro using propidium iodide staining and flow cytometry, ELISA, the Seahorse technique, and the fluorescent probes JC-1 and MitoSox. Results Islets from Zbed6 knockout mice showed lowered expression of the cell cycle gene Pttg1, decreased beta cell proliferation and decreased beta cell area, which occurred independently from ZBED6 effects on Igf2 gene expression. Zbed6 knockout mice, but not wild-type mice, developed glucose intolerance when given a high-fat diet. The high-fat diet Zbed6 knockout islets displayed upregulated expression of oxidative phosphorylation genes and genes associated with beta cell differentiation. In vitro, ZBED6 overexpression resulted in increased EndoC-βH1 cell proliferation and a reduced glucose-stimulated insulin release in human islets. ZBED6 also reduced mitochondrial JC-1 J-aggregate formation, mitochondrial oxygen consumption rates (OCR) and mitochondrial reactive oxygen species (ROS) production, both at basal and palmitate + high glucose-stimulated conditions. ZBED6-induced inhibition of OCR was not rescued by IGF2 addition. ZBED6 reduced levels of the mitochondrial regulator PPAR-γ related coactivator 1 protein (PRC) and bound its promoter/enhancer region. Knockdown of PRC resulted in a lowered OCR. Conclusions/interpretation It is concluded that ZBED6 is required for normal beta cell replication and also limits excessive beta cell mitochondrial activation in response to an increased functional demand. ZBED6 may act, at least in part, by restricting PRC-mediated mitochondrial activation/ROS production, which may lead to protection against beta cell dysfunction and glucose intolerance in vivo. Graphical abstract

scholarly journals BLUEBERRY JUICE AND ANTHOCYANINS MODULATE OBESITY, LEPTIN AND BETA CELL FUNCTION IN MICE FED A HIGH FAT DIET

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Ronald L. Prior ◽  
S. Wilkes ◽  
T. Rogers ◽  
R. C. Khanal ◽  
X. Wu ◽  
...  
Keyword(s):  
Beta Cell ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Fat ◽  
Blueberry Juice

Nr4a1 and Nr4a3 Knock Out Mice Have Impaired Glucose Clearance and Beta-Cell Function under High-Fat Feeding

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2040-P
Author(s):  
COURTNEY J. SMITH ◽  
KYLE B. KENER ◽  
JEFFERY S. TESSEM
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Fat ◽  
Knock Out ◽  
Glucose Clearance ◽  
Knock Out Mice ◽  
Fat Feeding
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