Long-term Glucose Homeostasis Research Articles

The impact of slowly digestible and resistant starch on glucose homeostasis and insulin resistance.

This review will summarize recent studies assessing the effect of slowly digestible starch (SDS) and resistant starch (RS) on glucose metabolism in healthy, prediabetic or type 2 diabetic adults. Currently, a particular interest in starch and its digestibility has arisen, with data showing a positive effect of SDS and RS on the glucose homeostasis of healthy, at-risk, prediabetic and type 2 diabetic patients but research is ongoing. Carbohydrates (CHO) and especially starch play a major role in the prevention and management of metabolic diseases such as type 2 diabetes (T2D). This largely depends on the quality and the digestibility (rate and extent) of the ingested starchy products, beyond their quantity. SDS have been poorly studied but display a beneficial effect on reducing glucose excursions in healthy and insulin-resistant subjects and a relevant potential to improve glucose control in type 2 diabetic individuals. As for RS, the results appear to be encouraging but remain heterogeneous, depending the nature of the RS and its role on microbiota modulation. Further studies are needed to confirm the present results and investigate the potential complementary beneficial effects of SDS and RS on long-term glucose homeostasis to prevent cardiometabolic diseases.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring.

Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic responses. In male offspring, while post-weaning HF led to impaired fasting glucose and worse glucose tolerance (p < 0.05), MCS in HF dams (HFCS) attenuated these changes. HFCS (versus maternal normal fat control) appeared to improve metabolic functioning of visceral adipose tissue during post-weaning HF feeding, preventing the elevation in leptin and increasing (p < 0.05) mRNA expression of insulin receptor substrate 1 (Irs1) that promotes peripheral insulin signaling in male offspring. In contrast, MCS had minimal effects on metabolic outcomes of female offspring. In conclusion, MCS during HF feeding in mice improves long-term blood glucose homeostasis in male offspring when they are faced with a postnatal obesogenic environment.

Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory

Stringent glucose demands render the brain susceptible to disturbances in the supply of this main source of energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments may arise from disturbed glucose regulation remains unclear. Here we show that chronic social defeat (CSD) stress in adult male mice induces hyperglycemia and directly affects spatial memory performance. Stressed mice developed hyperglycemia and impaired glucose metabolism peripherally as well as in the brain (demonstrated by PET and induced metabolic bioluminescence imaging), which was accompanied by hippocampus-related spatial memory impairments. Importantly, the cognitive and metabolic phenotype pertained to a subset of stressed mice and could be linked to early hyperglycemia 2 days post-CSD. Based on this criterion, ∼40% of the stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance of this biomarker emerges from the effects of the glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because upon dietary treatment, mice identified as having high glucose demonstrated restored spatial memory and normalized glucose metabolism. Conversely, reducing glucose levels by empagliflozin in mice that did not display stress-induced hyperglycemia (resilient mice) impaired their default-intact spatial memory performance. We conclude that hyperglycemia developing early after chronic stress threatens long-term glucose homeostasis and causes spatial memory dysfunction. Our findings may explain the comorbidity between stress-related and metabolic disorders, such as depression and diabetes, and suggest that cognitive impairments in both types of disorders could originate from excessive cerebral glucose accumulation.

Long-term (with and without caffeine) coffee consumption and glucose homeostasis

Long-term (with and without caffeine) coffee consumption and glucose homeostasis

Maternal low-protein diet during lactation combined with early overfeeding impair male offspring's long-term glucose homeostasis.

The early-life nutritional environment affects long-term glucose homeostasis, we investigated the effects of maternal low-protein diet combined with postnatal early overfeeding on the male offspring's glucose homeostasis in adulthood. Only male rats were used, and their delivery was considered postnatal-day 0 (PN0). Wistar rats' dams were divided into control (NP) or low-protein diet (LP). LP dams remained on the diet until PN14, after which all animals were supplied with the control diet. At PN2, litters were adjusted to 9 (control-NL) or 3 (postnatal-overfeeding-PO) pups, resulting in four experimental groups: NP-NL, NP-PO, LP-NL, and LP-PO. Litters were weaned on PN21. At PN80, a batch of animals from all experimental groups underwent surgery for cannula implantation, followed by intravenous glucose tolerance test (ivGTT), but the insulinogenic index (ISI) was calculated. At PN81, animals were euthanized and tissues were collected. LP-diet and early postnatal-overfeeding were effective in promoting the expected biometric outcomes at PN21 and PN81, but the LP-PO animals present a biometric profile similar to the control (NP-NL) group. Postnatal-overfeeding increased fasting glycemia in LP-PO animals (p < 0.01). In the ivGTT, postnatal-overfeeding elevated the glycemia (p < 0.0001), exacerbated in LP-PO animals (p < 0.0001). Insulinemia was reduced by both, maternal LP-diet and postnatal-overfeeding, with a higher degree of reduction in LP-PO animals (p < 0.0001). Maternal LP-diet and postnatal-overfeeding reduced the ISI (p < 0.0001). Factors interaction lead the LP-PO to a lower ISI compared to all other groups (p < 0.0001). The combination of low-protein diet in breastfeeding dams with postnatal overfeeding disturbed the offspring's glucose metabolism in adulthood.

Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study.

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age>18years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2±8.3years, BMI 24.9±3kg/m2, mean duration of HIV infection of 8.1±5.3years) were included. Baseline HbA1c was 4.4±0.4% and baseline presence of BactDNA in six patients. After 8.5±0.5years of follow-up, change in HbA1c was 1.5±0.47% in patients with BactDNA vs 0.87±0.3% in the rest of the sample p<0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis.

Diabetes and other endocrine-metabolic abnormalities in the long-term follow-up of pancreas transplantation.

Pancreas transplantation (PTX) has been demonstrated to restore long-term glucose homeostasis beyond what can be achieved by intensive insulin therapy or islet transplants. Moreover, PTX has been shown to decrease the progression of the chronic complications of diabetes. However, PTX patients require chronic use of immunosuppressive drugs with potential side effects. The long-term follow-up of PTX patients demands special care regarding metabolic deviations, infectious complications, and chronic rejection. Diabetes and other endocrine metabolic abnormalities following transplantation are common and can increase morbidity and mortality. Previous recipient-related and donor-related factors, as well as other aspects inherent to the transplant, act together in the pathogenesis of those abnormalities. Early recognition of these disturbances is the key to timely treatment; however, adequate tools to achieve this goal are often lacking. In a way, the type of PTX procedure, whether simultaneous pancreas kidney or not, seems to differentially influence the evolution of endocrine and metabolic abnormalities. Further studies are needed to define the best approach for PTX patients. This review will focus on the most common endocrine metabolic disorders seen in the long-term management of PTX: diabetes mellitus, hyperlipidemia, and bone loss. The authors here cover each one of these endocrine topics by showing the evaluation as well as proper management in the follow-up after PTX.

Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring

Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p < 0.05). The expression of POMC and MC4R genes were significantly increased in offspring exposed to FS diet during gestation, lactation and into 32-week age (p < 0.05). Consistently, hypomethylation of POMC promoter in the hypothalamus occurred in the FS diet offspring (p < 0.05), compared with the C group. However, no methylation was detected of MC4R promoter in both the two groups. Furthermore, POMC-specific methylation (%) was negatively associated with glucose response to a glucose load (r = -0.273, p = 0.039). Maternal and post-weaning high-fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline–ethanol blends

The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long–Evans rats were exposed for 6.5h/day on days 9–20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000ppm of E0 or E85 gained more weight per gram of food consumed during the 12days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27–29 and PND 56–63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose homeostasis). These observations suggest a LOEL of 3000ppm of E85 for vertical activity, LOELs of 9000ppm of E0 and E85 for maternal food consumption, and NOELs of 9000ppm for the other endpoints reported here. The ethanol content of the vapors did not consistently alter the pattern of behavioral, immunological, or physiological responses to the fuel vapors. The concentrations of the vapors used here exceed by 4–6 orders of magnitude typical exposure levels encountered by the public.

Perinatal exercise improves glucose homeostasis in adult offspring

Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring.

Evaluation of long-term glucose homeostasis in lean and obese cats by use of continuous glucose monitoring

To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS). 6 lean and 8 long-term (> 5 years) obese cats. Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS. Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats. Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

Extending the reach of Exendin-4: new pathways in the control of body weight and glucose homeostasis.

Extending the reach of Exendin-4: new pathways in the control of body weight and glucose homeostasis.

Multiple Intravenous Transplantations of Mesenchymal Stem Cells Effectively Restore Long-Term Blood Glucose Homeostasis by Hepatic Engraftment and β-Cell Differentiation in Streptozocin-Induced Diabetic Mice

Depletion of pancreatic β-cells results in insulin insufficiency and diabetes mellitus (DM). Single transplantation of mesenchymal stem cells exhibits short-term effects in some preclinical studies. Here, we further investigated the long-term therapeutic effects of multiple intravenous MSC transplantations. In this study, multiple human MSC transplantations (4.2 × 10(7) cells/kg each time) were performed intravenously at 2-week intervals into streptozocin (STZ)-induced diabetic mice for 6 months. Blood sugar, insulin, renal function, cholesterol, and triglyceride levels were monitored. We demonstrated that compared to single intravenous transplantation, which only transiently decreased hyperglycemia, multiple MSC transplantations effectively restored blood glucose homeostasis. Systemic oxidative stress levels were reduced from the seventh week of treatment. From the 11th week, production of human insulin was markedly increased. When MSC transplantation was skipped after blood sugar level returned to normal at the end of 15th week, a sharp rebound of blood sugar occurred, and was then controlled by subsequent transplantations. At the end of 6 months, histopathology examination revealed MSCs specifically engrafted into liver tissues of the recipients. Fifty-one percent of human cells in the recipient liver coexpressed human insulin, especially those surrounding the central veins. Taken together, intravenous MSC delivery was safe and effective for blood glucose stabilization in this preclinical DM model. Multiple transplantations were essential to restore and maintain glucose homeostasis through decreasing systemic oxidative stress in the early stage and insulin production in the late stage. Liver engraftment and differentiation into insulin-producing cells account for the long-term therapeutic effects of MSCs.

Refractory and new-onset diabetes more than 5 years after gastric bypass for morbid obesity

Few studies about long-term glucose homeostasis in bariatric patients are available. In a prospective protocol that included retrospective information, outcome of patients with both impaired and normal fasting blood glucose (FBG) was monitored to assess frequencies and correlates. Patients submitted to Roux-en-Y gastric bypass were classified as group I, elevated FBG, and group II, normal controls. Those in group I with improvement in FBG were defined as responsive and the others as refractory. Group II participants progressing to new-onset diabetes (NOD) or prediabetes represented NOD cases; the remaining were listed as stable controls. FBG was the main endpoint, but HbA1c results were considered, along with diet composition and general biochemical profile. Among 97 selected patients, 51 belonged to group I (52.4 ± 10.5 years, 29.6 % males, initial body mass index (BMI) 58.4 ± 13.4, current BMI 35.1 ± 8.4 kg/m(2)) and 46 to group II (48.2 ± 10.5 years, 19.6 % males, initial BMI 55.5 ± 8.8, current BMI 33.9 ± 6.9 kg/m(2)). Follow-up was 7-9 years, and 31.4 % (16/51) of group I were classified as refractory, whereas 15.2 % (7/46) of the controls converted to NOD. Multivariate analysis pointed out higher current BMI, older age, consumption of antidiabetic drugs, and male gender as features of refractory cases, whereas NOD participants were not significantly different from non-progressing controls. This is the first investigation, to the best of our knowledge, to underscore the correlates of refractory and NOD within the bariatric context. Further studies are recommended as such information could be valuable for patient selection, prognostic scoring, and outcome monitoring.

Biological Timekeeping in Obesity and Diabetes

Circadian systems are programmed by a transcription‐translation feedback loop that generates daily cycles of energy storage and utilization in synchrony with the 24 hr rotation of the Earth. In mammals, master pacemaker neurons located within the suprachiasmatic nucleus are entrained to light, and generate 24 hr oscillations in extra‐SCN neurons and most peripheral tissues, including those involved in glucose and lipid metabolism. During wakefulness and feeding, the molecular clock promotes glucose‐stimulated insulin secretion within b‐cells of the Islets of Langerhans. Clock ablation limited to pancreas results in hypoinsulinemic diabetes, indicating a primary function of peripheral clocks in glucose homeostasis. In contrast, ablation of the liver clock impairs oxidative metabolism, indicating that peripheral tissue clocks exert opposing effects in response to feeding and fasting. At the molecular level, clock disruption causes reduced NAD+ biosynthesis and leads to alterations in function of NAD+‐dependent ribosylases and de‐acetylases involved in oxidative metabolism. Circadian systems thus contribute to long‐term energy and glucose homeostasis across alternating behavioral and nutrient states.

Association between glycosylated haemoglobin A 1c and endothelial function in an adult non-diabetic population

Objective Endothelial dysfunction precedes apparent atherosclerosis in humans and is associated with a number of cardiovascular risk factors, including Type 2 diabetes. To investigate the impact of long-term glucose homeostasis on endothelial function in an adult non-diabetic population, we analysed the association of serum HbA 1c levels with endothelial function. Methods We studied cross-sectional data from 1384 subjects (696 women), aged 25–85, without diabetes, from the population-based Study of Health in Pomerania (SHIP-1). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) measurements of the brachial artery were performed using standardised ultrasound techniques. Linear regression models were carried out to assess the association between serum HbA 1c levels and FMD/NMD. Results Multivariable analyses disclosed an inverse association between serum HbA 1c levels and FMD in women, but not in men. In women without current use of antihypertensive medication, increasing serum HbA 1c levels were associated with decreasing FMD levels after adjustment for age, body mass index, smoking status, hypertension, low-density lipoprotein cholesterol, and sex-hormone medication ( β = −1.17; 95% CI −2.03; −0.30, p = 0.009). There was an inverse association between serum HbA 1c levels and NMD in men ( β = −1.68; 95% CI −2.83; −0.52, p = 0.005), but not in women. Conclusion We conclude that higher serum HbA 1c levels in non-diabetic subjects are inversely associated with FMD in women without antihypertensive medication, but not in men. The gender-specific aspects concerning the association of HbA 1c levels and NMD in this population should be investigated in further studies. Our results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA 1c are associated with subclinical cardiovascular diseases detected by FMD, especially in women.

Combination treatment of db/db mice with exendin-4 and gastrin preserves β-cell mass by stimulating β-cell growth and differentiation.

Aim/Introduction: Preservation of β-cell mass is crucial for maintaining long-term glucose homeostasis. Therapies based on incretin and its mimetics are expected to achieve this goal through various biological functions, particularly the restoration of β-cell mass. Here we tested the effects of gastrin and exendin-4 in type 2 diabetic animals. The effects of exendin-4 and gastrin on β-cell function and mass were examined in 8-week-old db/db mice. INS-1 beta cells and AR42J cells were used to determine the molecular mechanism underlying the effects of the two agents. Immunohistochemistry, western blotting and RT-PCR assays were used to assess the biological effects of the two agents. Two weeks of combination administration of exendin-4 plus gastrin resulted in a significant improvement of glucose tolerance associated with a marked preservation of β-cell mass in db/db mice. Immunohistochemical analysis showed that such treatment resulted in the appearance of numerous irregularly-shaped small islets and single insulin-positive cells. While gastrin had little biological effect on INS-1 β-cells consistent with low expression of its intrinsic receptor on these cells, it caused differentiation of AR42J cells into insulin-producing cells. Co-stimulation with exendin-4 significantly enhanced gastrin-induced endocrine differentiation of AR42J precursor cells. These findings were further supported by enhanced expression of key genes involved in β-cell differentiation and maturation, such as neurogenin3 (Ngn3) and MafA. These results suggest that combination treatment of db/db mice with exendin-4 and gastrin preserves β-cell mass by stimulating β-cell growth and differentiation. (J Diabetes Invest, doi: 10.1111/j.2040-1124.00044.x, 2010).

Maintenance of blood glucose level under intensive mental activities: episodic moderate drinkers versus non-drinkers

BackgroundThe benefits of alcohol, especially to the functioning ofthe hearth and circulatory system have always beenrecognized by many researchers world-wide [1]. Butbesides, these positive effects, alcohol use, even in mod-erate amounts can be detrimental under certain condi-tions. Several studies have recognized the hypoglycemiceffect of alcohol use in excessive doses. Centuries ago,Krebs and fellows admitted that acute alcohol intake inexcessive doses results in hypoglycemia [2,3]. However,little is still known about the aftereffects of alcohol atlow doses, even after a week’s interval of moderatedrinking.AimWe examine the efficiency of glucose homeostasis con-trol of non-drinkers and episodic moderate drinkers,after approximately one week interval of moderatedrinking and under intensive mental activities.Materials and methodsThe Ethics Committee approved the study protocoland informed consents were obtained from the volun-teers after the aims and objectives of the study hadbeen explained. The study took 6-hours (on fasting),involving male students (5 non-drinkers and 8 episodicmoderate drinkers that have abstained from alcoholdrinks of any composition for at least the last sevendays before the study). Blood glucose concentration(BGC) was measured at 2 hours interval, includinginitial BGC. Various questionnaires - AUDIT, texts andquestions, neuropsychological questionnaires, tests onvisual, auditory, operative short-term memory andattention (using Anfimov geometric tables) were usedas a measure. The Pearson and Student’st-testswereemployed for statistical analysis of results. The prob-ability value for significance was set at p < 0.05.ResultsSignificant decrease in the effectiveness of active atten-tion and a faster development of fatigue after 4-6 hoursof mental activities in episodic moderate drinkers, com-pared to non-drinkers was statistically proven. Disordersin episodic moderate drinkers are retained within a per-iod of 7-10 days after moderate alcohol use. The non-drinkers had increasing BGC in relation to their initiallevel in all phases of the experiment (ð < 0.001).Increase in BGC of alcohol users was observed onlywithin the first 2 hours (p < 0.05). Thereafter, a signifi-cant fall in BGC was observed in the 4-6 hrs of theexperiment in relation to the BGC of anon-drinkers andits level after 2 hours. Episodic moderate drinkers had26 times higher errors on various tests than the abstai-ners (p < 0.001). The errors made on various testsincreased with decrease in BGC (r = -0.83; p < 0.01).ConclusionsThis is the first study involving male volunteers to showthat alcohol use, even episodic (1-2 times/month) insmall doses (23 ± 8 ml/person/session), after 7-10 daysof alcohol intake, is accompanied by long-term glucosehomeostasis disorders, leading to cognitive function dis-turbances and a decrease in the effectiveness of mentalactivities. Significant decrease in BGC in episodic mod-

Effects of acute ethionine injection on plasma ghrelin and obestatin levels in trained male rats

Ghrelin and obestatin are orexigenic and anorexigenic peptides, respectively, that are secreted from the stomach mucosa into the circulation. These peptides have opposing actions on food intake, weight gain, and adiposity. It is thought that ghrelin is sensitive to a negative energy environment and also plays a considerable role in short- and long-term energy balance and glucose homeostasis. It has been suggested that the levels of ghrelin and obestatin are upregulated by fasting, hypoglycemic status, and a physical-exercise–induced energy deficit. Ethionine (ETH), the ethyl analogue of methionine, has been shown to increase food intake, decrease adenosine triphosphate (ATP) and glycogen levels, and inhibit protein synthesis in the liver. The purpose of this study was to examine the effect of a single dose of ETH (0.7 mg/g of body weight) injection on resting plasma total ghrelin and obestatin concentrations in male trained rats. Thirty-two adult Wistar male rats weighing 180 to 200 g were randomly assigned to control (n = 16) and training (n =16) groups. The training group was exercised for 10 weeks (25 m/min, 0% grade, 60 minutes, and 5 d/wk). Seventy-two hours after the last exercise session, rats were injected with either saline (NaCl) or ETH and then killed. Ethionine compared with a NaCl injection resulted in significant ( P < .013) reductions in resting hepatic ATP and glycogen levels, and in a significant ( P < .001) increase in concentrations of plasma total ghrelin but not obestatin. The results indicate that ETH-induced liver ATP and glycogen deficiency could exert a powerful regulatory influence on plasma total ghrelin, but this is not the case for obestatin. Findings demonstrate the short-term energy-regulating capacity of ghrelin.

Minireview: Posttranscriptional Regulation of the Insulin and Insulin-Like Growth Factor Systems

Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3' and 5' untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism.