Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats

Abstract

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Short‐ and medium‐term effects of light to moderate alcohol intake on glycaemic control in diabetes mellitus: a systematic review and meta‐analysis of randomized trials

“…Conversely, high alcohol consumption is reported to be a risk factor for diabetes . The mechanisms for this dual effect may be protection by improved insulin sensitivity at low to moderate doses and pancreatic damage at high doses ; there may also be a contribution from obesity caused by long‐term alcohol consumption . This work consolidates and extends previous literature , providing the best available evidence that there is no effect of short‐term or medium‐term moderate alcohol consumption on glycaemic control.…”

Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

“…However, the glucose levels of the OLETF group at postprandial 120 min were more than twice as high as those of the LETO group, demonstrating the typical phenomenon of impaired glucose metabolism in T2DM. In previous studies [9] , [16] , [22] , postprandial glucose levels of OLETF rats fed according to the same diet method used to induce diabetes were also higher than fasting glucose levels. Interestingly, the postprandial glucose levels of the prediabetes group were lowered to nearly fasting glucose levels, and levels in the prediabetes group exposed to ethanol were also lowered quickly compared to those of the diabetes group exposed to ethanol [9] .…”

“…T2DM, which is caused by metabolic disorders such as impaired glucose tolerance and insulin resistance, is worsened by chronic heavy alcohol abuse, resulting in an increase in cellular toxicity and dysfunction of the pancreas [9] , [24] . Therefore, in addition to the development of diabetes-targeted medicines, it is necessary to develop medicine for diabetics chronically exposed to alcohol.…”

“…Previous studies have observed that chronic heavy alcohol consumption leads to increases in blood glucose levels and insulin resistance in healthy controls as well as in patients with T2DM [6] , [7] . Recently, it was reported that the impairment of insulin production in the pancreas is caused by chronic alcohol use, leading to the development of T2DM as well as the onset of T2DM [8] , [9] . In the study of Lee et al [9] , endoplasmic reticulum stress markers in the pancreas increased after chronic exposure of early diabetic stage rats to ethanol, suggesting that pancreatic dysfunction mediated by the activation of the endoplasmic reticulum stress proapoptotic pathway by ethanol may accelerate the development of T2DM.…”

“…Recently, it was reported that the impairment of insulin production in the pancreas is caused by chronic alcohol use, leading to the development of T2DM as well as the onset of T2DM [8] , [9] . In the study of Lee et al [9] , endoplasmic reticulum stress markers in the pancreas increased after chronic exposure of early diabetic stage rats to ethanol, suggesting that pancreatic dysfunction mediated by the activation of the endoplasmic reticulum stress proapoptotic pathway by ethanol may accelerate the development of T2DM. Kim et al [8] found that chronic ethanol treatment of diabetic-like mice induced through a high-fat diet promoted a decrease in islet cell mass and insulin expression.…”