This study evaluates the relation of a Mediterranean dietary pattern and its individual components with the cardiovascular risk factors profile, plasma glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568 participants at 57 diabetes clinics. Diet was assessed with the EPIC (European Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to the Mediterranean diet was evaluated with the relative Mediterranean diet score (rMED). A high compared to a low score was associated with a better quality of diet and a greater adherence to the nutritional recommendations for diabetes. However, even in the group achieving a high score, only a small proportion of participants met the recommendations for fiber and saturated fat (respectively 17% and 30%). Nonetheless, a high score was associated with lower values of plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of the single food items components of the rMED score with the achievement of treatment targets for plasma lipids, blood pressure, glucose, and BMI were also explored. The study findings support the Mediterranean dietary model as a suitable model for type 2 diabetes and the concept that the beneficial health effects of the Mediterranean diet lie primarily in its synergy among various nutrients and foods rather than on any individual component.

The development of obesity is cornerstone in the etiology of metabolic and vascular insulin resistance and consequently exacerbates glycemic control. Exercise is an efficacious first-line therapy for type 2 diabetes that improves insulin action through, in part, reducing hormone mediated inflammation. Together, improving the coordination of skeletal muscle metabolism with vascular delivery of glucose will be required for optimizing type 2 diabetes and cardiovascular disease treatment.

Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.

Background:In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This review summarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To further understand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventions that can be used in future exercise-related studies.

Methods:PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treating various diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity [Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters: one that limited publication dates to"in 10 years"and one that sorted the results as"best match". Then we grouped the commonly used exercise methods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseases and organ functions in 8 different systems.

Results:A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exercise interventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascular system (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and the system related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntary wheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, most of them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless of the exercise method used, although some diseases showed the best remission effects when a specific method was used.

Conclusion:Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exercise interventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention compliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exercise interventions in humans.

OBJECTIVES: This randomized controlled study was conducted to determine the effect of low glycemic index (GI) dietary advice on eating patterns and dietary quality in Asian patients with type 2 diabetes (T2DM).

METHODS: Asian patients with T2DM (N =  104) were randomized into 2 groups that received either low GI or conventional carbohydrate exchange (CCE) dietary advice for 12 weeks. Nutritional prescriptions were based on the medical nutrition therapy for T2DM, with the difference being in the GI component of the carbohydrates. Dietaryintake and food choices were assessed with the use of a 3-day food record.

RESULTS: At week 12, both groups achieved the recommendations for carbohydrate (52 ± 4% and 54 ± 4% of energy) and fat (30 ± 4% and 28 ± 5% of energy) intake. There were no significant differences in the reported macronutrient intake in both groups. With the low GI diet, crude fiber and dietary calcium intake increased, while the dietary GI reduced. Subjects in the lowest dietary glycemic index/glycemic load (GI/GL) quartile consumed more parboiled/basmati rice, pasta, milk/dairy products, fruits, and dough, which are foods from the low GI category. There was a significant reduction in the hemoglobin A(1c) level at week 12 for patients in the lowest GI/GL quartile (Δ  =  -0.7 ± 0.1%) compared with those in the highest GI/GL quartile (Δ  =  -0.1 ± 0.2%).

CONCLUSIONS: These results demonstrate the ability of low GI dietary advice to improve the dietary quality of Asian patients with T2DM.

Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. Theα-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer's disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2-40 μg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruitingbody extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities.

BACKGROUND:Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments.

METHODS:Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined.

RESULTS:The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells.

CONCLUSIONS:Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.

AIM:The study aimed to assess the effect of exercise intervention on the management of obese T2DM patients.

METHODS:The literature retrieval was conducted in relevant databases from their inception to 2015, with predefined searching strategy and selection criteria. The Cochrane Collaboration's tool was utilized to assess the quality of included studies. Weighted mean difference (WMD) with its corresponding 95% CI (confidence interval) was used as the effect size.

RESULTS:A subset of 13 eligible studies was selected. Exercise significantly reduced the concentration of high sensitivity C reactive protein (4 months: WMD=-1.03, 95% CI: -1.77 to -0.29, P<0.01), triglyceride (6 months: WMD=-24.75, 95% CI: -27.67 to -21.83, P<0.01), diastolic blood pressure (6 months: WMD=-2.70, 95% CI: -4.12 to -1.28, P=0.0002), systolic blood pressure (WMD=-7.98, 95% CI: -9.87 to -6.08, P<0.01)), HbA1c (4 months: WMD=-0.25, 95% CI: -0.49 to -0.02, P=0.04) and homeostasis model assessment-insulin resistance (3 months: WMD=-0.19, 95% CI: -0.37 to -0.01, P=0.04); and a pronounced increase of HDL-C (12 months: WMD=3.57, 95% CI: 1.92 to 5.21, P<0.01).

CONCLUSION:Exercise was beneficial to obese T2DM patients.

AIMS/BACKGROUND: R (+)-alpha-lipoic acid (RLA) has been suggested for the treatment of liver diseases, but has also been shown to improve glucose utilization in diabetic patients. Because detailed information of RLA action on carbohydrate metabolism in intact liver is lacking, we examined concentration-dependent effects of RLA on hepatic glucose production. METHODS: RLA (10(-6-)10(-3) mol L(-1)) or buffer (control) was infused in isolated livers of fasted rats during recirculating perfusion for 90 min (n = 4-6/group). Hepatic glucose and lactate fluxes and bile secretion were continuously monitored. RESULTS: RLA reduced lactate (10 mmol L(-1))-dependent glucose production in concentration-dependent fashion (R = - 0.780, P<0.001) by up to 67% compared with control (0.36 +/- 0.02 micromol min(-1) g(-1)). In parallel, RLA dose dependently decreased lactate uptake (R = - 0.592, P<0.001) also by up to 67% (control: 0.58 +/- 0.08 micromol min(-1) g(-1)). RLA (10(-4) mol L(-1) and 10(-3) mol L(-1)) stimulated bile flow by approximately 20 and approximately 50%, respectively (P<0.02 vs. control). After 10(-3) mol L(-1) RLA infusion, liver glycogen was approximately 3 fold higher (5.2 +/- 1.1 vs. control: 1.8 +/- 0.2 micromol g(-1), P<0.002). Also at low lactate concentrations (1 mmol L(-1)), 10(-3) mol L(-1) RLA reduced glucose production by approximately 53% and lactate uptake by approximately 60%, but stimulated bile secretion by approximately 50% (P<0.05). CONCLUSION: RLA reduces hepatic glucose release by inhibiting lactate-dependent glucose production in a concentration-dependent fashion.

Efficacious adherence to treatment protocol predicts metabolic control among Type 2 diabetics (T2DM) [1-4]; however, few healthcare systems employ individualized strategies to mediate the comorbidity of T2DM with other chronic disease states. A clinically prescribed ketogenic diet, patient-centered nutritional education and high intensity interval training (HIIT), girded by solution-focused psychotherapy, modulate significant improvements in the clinical biomarkers associated with concurring T2DM and clinical depression [5-15]. Relevant metabolic change was noted in the following measures: HOMA-IR, triglyceride/HDL ratio, HgA1c, fasting insulin, fasting glucose, fasting triglycerides, LDL, VLDL, HDL, total cholesterol and C-reactive protein. The Patient Health Questionnaire 9 (PHQ-9) along with clinical interview and the mental status exam showed notable change in the patient's depressive symptoms; likewise, her self-efficacy score normalized, as measured by the General Self-Efficacy Questionnaire (GSE) and the Metabolic Syndrome Compliance Questionnaire (MSC). The case study highlights a 65-year old female who presented with a 26-year history of dually-diagnosed Type 2 diabetes (T2DM) and major depressive disorder (MDD). The patient was prescribed a ketogenic diet (KD), clinically formulated from her resting metabolic rate, body fat percentage and lean body mass, together with weekly nutrition education, high intensity interval training (matched to her cardiovascular conditioning), and eight 45-minute solution-focused psychotherapy sessions. Intervention goals included improved insulin sensitivity evaluated by the HOMA-IR, sustained glycemic control measured via HgA1c, reduced cardiovascular risk via the triglyceride/HDL ratio, and improved depressive symptoms with increased self-efficacy monitored by the PHQ-9 and GSE/MSC. The results of the 12-week intervention were statistically significant. The patient's HgA1c dropped out of diabetic range (8.0%) and normalized at 5.4%. Her average daily glucose measurements declined from 216 mg/dL to 96 mg/dL; the HOMA-IR and triglyceride/HDL ratios improved by 75%. Her marker for clinical depression and measurement of self-efficacy normalized. The 12-week individualized treatment intervention served to functionally reverse 26 years of T2DM, ameliorate two and half decades of chronic depressive disorder and empower/equip the patient with a new experience of hope and success.

The aim was to assess the long-term effect of a loose restriction of carbohydrate intake (carbohydrate-reduced diet: CARD) compared to a conventional diet (CD) in type 2 diabetes. One hundred and thirty-three type 2 diabetic outpatients followed the CD (n=57, 1734+/-410 kcal, carbohydrate:protein:fat ratio=57:16:26) or CARD (n=76, 1773+/-441 kcal, carbohydrate:protein:fat ratio=45:18:33) according to their own will, and were followed up for 2 years. Glycemic control, body mass index (BMI), serum cholesterols and dose of antidiabetic drugs were assessed at baseline and after 1 and 2 years. At baseline, hemoglobin A1c (HbA1c) and BMI levels were 7.1+/-1.0% and 24.2+/-2.9, respectively, in the CD group, and 7.4+/-1.1% and 25.1+/-3.4 in the CARD group, showing no significant differences. During the 2-year follow-up period, HbA1c levels were significantly improved in the CARD group (CD: 7.5+/-1.3%, CARD: 6.7+/-0.6%, P<0.001), and BMI decreased more significantly in the CARD group (CD: 23.8+/-3.0, CARD: 23.8+/-3.5, P<0.001). The doses of sulfonylureas clearly tapered, and serum cholesterol profiles improved significantly with the CARD. Our results warrant a long-term and large-scale randomized study of the diet for type 2 diabetes.

Foot ulcers are serious complications of diabetes mellitus (DM) and are known to be resistant to conventional treatment. This study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of 30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than 6 weeks duration with negative culture were studied. Patients were randomized into two groups of 15 each. Patients in study group received LLLT (660 ± 20 nm, 3 J/cm(2)) along with conventional therapy and those in control group were treated with conventional therapy alone. The primary outcomemeasure was the absolute and relative wound size reduction at 2 weeks compared to the baseline parameter. Percentage ulcer area reduction was 37 ± 9% in the LLLT group and 15 ± 5.4% in the control group (p < 0.001). For ∼75% of wounds of the treatment group, wound area reduction of 30-50% was observed. In contrast, for the control group, ∼80% of wounds showed a wound area reduction of<20% on day 15. Further, the wounds with initial wound area 1000-2000 mm(2) seems to have better final outcome than the groups with larger areas. The treated groups showed higher amount of granulation than the control group. The results suggest that LLLT is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.

The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba). The acute effects of exercise were examined by means of a single session of Joba riding that lasted for 30 min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba apparatus. The insulin sensitivity was determined pre- and post-training by a 90 min euglycemic clamp. In the acute study, average GIR during exercise was significantly higher than pre-exercise (7.8+/-0.4 versus 5.2+/-0.3 mg kg(-1)min(-1), P<0.01) and average GIR during recovery decreased to almost the same levels of pre-exercise (5.0+/-0.4 mg kg(-1)min(-1); P<0.01). The 12-week training resulted in a significant increase in the steady-state GIR (from 5.2+/-0.3 to 7.4+/-0.8 mg kg(-1)min(-1); P<0.05). The steady-state GIR after 12 weeks of detraining returned to pre-training levels (5.3+/-0.5 mg kg(-1)min(-1); P<0.05). In elder diabetic patients, mechanical horseback riding enhances the insulin-induced glucose uptake.

Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

Background:Previous research indicates that patients with type 2 diabetes are at higher risk of becoming frail. Emerging evidence also indicates that the Mediterranean diet may prevent frailty in the older population.

Objective:The aim of this study was to assess whether a Mediterranean-style diet pattern was associated with lower risk of frailty among older women with diabetes.

Design:This was a prospective cohort study in 8970 women aged≥60 y with type 2 diabetes from the Nurses' Health Study. Adherence to the alternate Mediterranean diet (aMED) score was first measured in 1990 and repeated every 4 y until 2010. Frailty occurrence was ascertained up to 2012 and was defined as having ≥3 of the following 5 criteria from the fatigue, resistance, aerobic, illnesses, loss of weight (FRAIL) scale: Fatigue, low Resistance, low Aerobic capacity, having ≥5 Illnesses, and weight Loss of ≥5%. Those with frailty at baseline were excluded.

Results:During follow-up, we identified 569 incident cases of frailty. After adjustment for lifestyle factors and medication use, the HR (95% CI) of frailty was 1 for the lowest quartile of the aMED score, 0.88 (0.71, 1.10) for the second quartile, 0.69 (0.53, 0.88) for the third quartile, and 0.54 (0.42, 0.71) for the highest quartile (P-trend<0.001). A 2-point (∼1 SD) increase in the aMED score was associated with a 28% (95% CI: 19%, 36%) reduced risk of frailty. The largest reduction in the risk was observed for a higher consumption of vegetables and fruit, as well as for alcohol intake.

Conclusions:A Mediterranean-style diet pattern was associated with reduced risk of frailty syndrome in older women with type 2 diabetes.

BACKGROUND AND AIMS:Endothelial dysfunction (ED) plays a key role in the development of atherosclerotic cardiovascular disease (ASCVD). Likewise, type 2 diabetes (T2D) is a major CVD risk factor. Therefore, our objective was to explore whether long-term consumption of a Mediterranean diet (MedDiet) rich in olive oil or a low-fat diet (LF diet) was associated with an improvement in ED and whether the potential benefits were similar in patients with or without T2D in the CORDIOPREV clinical trial (NCT00924937).

METHODS:Endothelial function was measured in 805 participants who had completed follow-up ultrasound image studies, using ultrasonography of brachial artery to calculate flow mediated vasodilatation (FMD) before and after 1.5 years of intervention with a MedDiet [35% of calories from fat (22% monounsaturated) and 50% from carbohydrates] and LF diet [28% fat (12% monounsaturated) and 55% of calories from carbohydrates]. We categorized participants as patients with T2D, prediabetes, and without T2D according to the American Diabetes Association (ADA) criteria.

RESULTS:MedDiet increased FMD in patients with T2D [5.2 ± 0.4 at 1.5 years vs. 3.8 ± 0.4 at baseline; p=0.04] and prediabetes [4.9 ± 0.4 vs. 3.8 ± 0.4; p=0.04] and induced an improvement in FMD compared to LF diet in patients with diabetes [5.2 ± 0.4 (MedDiet) vs.3.7 ± 0.4 (LF diet); p=0.01]; whereas both diets maintained FMD stablein patients without diabetes.

CONCLUSIONS:Habitual consumption of a MedDiet rich in extra virgin olive oil improves endothelial function in patients with prediabetes and diabetes. This takes great importance given that diet must be the cornerstone of treatment of patients with diabetes at high cardiovascular risk.

Diabetes Mellitus type 2 (DM2) is a metabolic disease that develops by a decrease in sensitivity of insulin receptors as an effect of the disruption certain metabolic functions in the processing of glucose. DM2 patients have, uncontrolled glucose levels, and commonly have problems with obesity and cardiovascular disease. Patients are treated with standard diet, insulin, diabetic oral agents and antihypertensive drugs, but this approach does not completely stops tissue deterioration since it does not address the metabolic root of the disease. Metabolic correction is proposed as a suitable adjunct treatment to improve clinical outcomes. Metabolic correction is based on diet modification, proper hydration and scientific supplementation directed to improve cellular biochemistry and metabolic efficiency. In addition, other possible benefits may include reduction in medication use, disease complications and medical costs. To test the results of a metabolic correction program, 25 patients with DM2 participated in an education program about adequate food consumption that promoted control of blood glucose levels. Anthropometric measurements and blood tests were performed during a 13 week program based on a low carbohydrate diet, proper hydration and magnesium supplementation. The metabolic correction program implemented by a proprietary educational system resulted in significant reductions in glucose, triglycerides, cholesterol, weight and waist circumference. Improvements in these values could represent an important reduction of coronary heart disease risk factors as well as other chronic degenerative diseases. In addition there was medication dosage reduction in one or more medications in 21 of the 25 participating patients, which suggest that the program has the potential to improve health outcomes and reduce health care costs.

AIMS/HYPOTHESIS:Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals.

METHODS:The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated.

RESULTS:OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats.

CONCLUSIONS/INTERPRETATION:Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.