The irreversible loss of estrogen (specifically 17-β-estradiol; E2) compromises whole-body glucose tolerance in women. Hormone replacement therapy (HRT) is frequently prescribed to treat estrogen deficiency, but has several deleterious side effects. Exercise has been proposed as an HRT substitute, however, their relative abilities to treat glucose intolerance are unknown. Thirty ovariectomized (OVX) and 20 SHAM (control) rats underwent glucose tolerance tests (GTT) 10 weeks post surgery. Area under the curve (AUC) for OVX rats was 60% greater than SHAM controls (P = 0.0005). Rats were then randomly assigned to the following treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5×/weeks), OVX sed, ex, or E2 (28 μg/kg bw/day) for 4 weeks. OVX ex rats experienced a ∼45% improvement in AUC relative to OVX sed rats, whereas OVX E2 underwent a partial reduction (17%; P = 0.08). Maximal insulin-stimulated glucose uptake in soleus and EDL was not impaired in OVX rats, or augmented with exercise or E2. Akt phosphorylation did not differ in soleus, EDL, or liver of any group. However, OVX ex and OVX E2 experienced greater increases in p-Akt Ser473 in VAT and SQ tissues compared with SHAM and OVX sed groups. Mitochondrial markers CS, COXIV, and core1 were increased in soleus posttraining in OVX ex rats. The content of COXIV was reduced by 52% and 61% in SQ of OVX sed and E2 rats, compared to SHAM controls, but fully restored in OVX ex rats. In summary, exercise restores glucose tolerance in OVX rats more effectively than E2. This is not reflected by alterations in muscle maximal insulin response, but increased insulin signaling in adipose depots may underlie whole-body improvements.

BackgroundWe recently demonstrated that feeding a natural CLAt10,c12-enriched butter to lean female rats resulted in small, but significant increases in fasting glucose and insulin concentrations, and impaired insulin tolerance. Our goal was to extend these findings by utilizing the diabetes-prone female fatty Zucker rat. Rats were fed custom diets containing 45 % kcal of fat derived from control and CLAt10,c12-enriched butter for 8 weeks.MethodsCLA t10,c12-enriched butter was prepared from milk collected from cows fed a high fermentable carbohydrate diet to create subacute rumen acidosis (SARA); control (non-SARA) butter was collected from cows fed a low grain diet. Female fatty Zucker rats (10 weeks old) were randomly assigned to one of four diet treatments: i) low fat (10 % kcal), ii) 45 % kcal lard, iii) 45 % kcal SARA butter, or iv) 45 % kcal non-SARA butter. A low fat fed lean Zucker group was used as a control group. After 8 weeks, i) glucose and insulin tolerance tests, ii) insulin signaling in muscle, adipose and liver, and iii) metabolic caging measurements were performed.ResultsGlucose and insulin tolerance were significantly impaired in all fatty Zucker groups, but to the greatest extent in the LARD and SARA conditions. Insulin signaling (AKT phosphorylation) was impaired in muscle, visceral (perigonadal) adipose tissue and liver in fatty Zucker rats, but was generally similar across dietary groups. Physical activity, oxygen consumption, food intake and weight gain were also similar amongst the various fatty Zucker groups.ConclusionsIncreasing the consumption of a food naturally enriched with CLAt10,c12 significantly worsens glucose and insulin tolerance in a diabetes-prone rodent model. This outcome is not explained by changes in tissue insulin signaling, physical activity, energy expenditure, food intake or body mass.

IntroductionLoss of estrogen in females increases the risk for insulin resistance. Hormone replacement therapy (HRT) is often prescribed to treat estrogen deficiency but has several detrimental side effects. Exercise is suggested as an HRT substitute since it improves insulin sensitivity, but the efficacy of exercise vs. HRT on glucose tolerance is unknown. The purpose of this study was to compare exercise training to 17‐β‐estradiol (E2) supplementation on restoring glucose tolerance (GT) in ovariectomized (OVX) rats.Methods30 OVX and 20 SHAM rats consumed a phytoestrogen free diet, ad libitum. Glucose tolerance tests (GTT) were performed at 10 weeks. Blood samples were drawn to assess serum insulin. Rats were randomly assigned to one of five 4 week treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5x/wk), OVX sed, ex or E2 (28 ug/kg/day). GTTs and blood sampling were repeated at 15 weeks. Glucose uptake in soleus and EDL muscle was assessed, and basal and maximal insulin‐stimulated EDL, soleus, adipose and liver samples were frozen for analysis.ResultsOVX rats were glucose intolerant at 10 weeks relative to SHAMs. After treatment, GT in OVX ex rats was entirely recovered, but only partially in OVX E2 rats. Insulin secretion at 15 min. during the 15 week GTT was significantly higher in OVX sed vs. OVX E2 or ex groups; however maximal insulin‐stimulated glucose uptake in soleus or EDL was unaffected.ConclusionsExercise restores GT in OVX rats more effectively than E2. Whole‐body improvements are not reflected by alterations in muscle maximal insulin response. This suggests adipose or liver as primary effectors of E2 or exercise treatment in OVX rats.Supported by NSERC