Fish Oil–Enriched Diet and Reduction of Low-Dose Streptozocin–Induced Hyperglycemia: Inhibition of Macrophage Activation

Abstract

Repeated low doses of streptozocin (STZ; 40 mg/kg, 5 injections/day) induce hyperglycemia in certain strains of mice after a latency of 1 wk. Omega-3 polyunsaturated fatty acids (omega 3FA) have been reported to suppress immune processes by blockade of the cyclooxygenase pathway of arachidonic acid metabolism. We investigated the effects of diets high in omega 3FA on the development of diabetes in the low-dose STZ-induced diabetes (LDSTZ-D) model. Male C57BL/6J mice were on a fish oil diet (FOD) as a source of omega 3FA 8 wk before STZ injection. Controls received laboratory chow only or a coconut oil diet (COD). Blood glucose levels in FOD mice were reduced (12.5 vs. 28 mM for COD mice, P less than .001) 60 days after STZ injection with a diet in which 20% of the calories were from fish oil. In FOD mice, immunohistology showed reduced numbers of class II antigen-expressing cells in pancreatic islets followed by a decreased extent of insulitis. FOD significantly decreased the number of Fc receptor-negative dendritic cells in cytospin preparations of islets isolated from diabetic mice. Interleukin 1-like activity of peritoneal exudate cell supernatants isolated from mice on FOD was reduced. FOD did not improve insulin secretion of isolated islets from LDSTZ-D mice. These data indicate a beneficial effect of FOD on the immune component of the mouse LDSTZ-D model.

n-3 Fatty Acids in the Treatment of Diabetic Patients

“…Here pretreatment of an insulin-secreting rat insulinoma cell line with ␣-LNA, EPA, and DHA prevented alloxan-induced cytotoxicity, although these fatty acids were less effective than LA (18:2 n-6) and ␥-LNA (18:3 n-6). This study supports and extends previous findings that n-6 fatty acids (mostly AA) can also prevent alloxan-induced type 1 diabetes in experimental animals (59) In vivo animal studies The hypothesis that an increased intake of n-3 fatty acids might reduce the risk of developing diabetes has been tested in mice, where supplementation with fish oil inhibited hyperglycemia and pancreatic insulitis in streptozocin-induced diabetes (60). A major advance has been made with the use of the hyperinsulinemic, euglycemic clamp technique in chronically cannulated rats receiving 2-deoxyglucose.…”

Eicosanoids, β-cell function, and diabetes

“…These novel studies [161; 162] demonstrate that endogenously synthesized ω-3 PUFAs are β-cell protective. Similarly, an earlier study has demonstrated that ω-3 PUFA-enriched diet reduces hyperglycemia in STZ diabetes [163]. Moreover, ω-3 PUFAs intake alleviates obesity-induced insulin resistance and hepatic steatosis through upregulation of insulin sensitivity related genes, such as glucose transporter-2 and −4, insulin receptor substrate-1 and −2 [164] and intake of ω-3 PUFA-rich diet prevents obesity [165] and improves insulin sensitivity [166].…”

Transgenic expression of n‐3 fatty acid desaturase (fat‐1) in C57/BL6 mice: Effects on glucose homeostasis and body weight

“…Since there as no change in insulin sensitivity, we hypothesize that there might be a better insulin response in the pancreatic β-cell. Because fish oil protects β-cells in mice from the toxicity of a low dose streptozotocin [Linn et al, 1989], n -3 fatty acids may preserve insulin section by protecting β-cell in male mice fed the HCD. In contrast, reduction in insulin secretary response was suggested in female fat-1 transgenic mice eating the HCD.…”