Blood Glucose Disposal Research Articles

Peripheral Heating With Negative Pressure at the Feet Increases Blood Flow at the Popliteal, Brachial, and Carotid Arteries

The prevalence of diabetes continues to increase with half (53%) of American adults having some form of diabetes mellitus as of 2020. Novel therapies could help prevent and manage diabetes and its complications. Applying heat with negative pressure (HNP) to the extremities decreases postprandial blood glucose through unknown mechanisms. Increased blood flow to peripheral tissues during HNP may facilitate greater disposal of blood glucose. Objective: Examine the effects of HNP on arterial blood flow in the popliteal, brachial, and carotid arteries. Hypothesis: HNP will increase popliteal but not brachial or carotid blood flow. Methods: Heat (42°C) and negative pressure (-75mmHg) were applied to the soles of both feet and from the feet to calves, respectively. An ultrasound doppler (Philips CX50, USA) was used to measure time-averaged mean velocity (TAMV) and vessel cross-sectional area (CSA) in the left or right popliteal, brachial, and carotid arteries before and during HNP. Body composition was determined via bioelectrical impedance analysis (Inbody 770, Korea). Blood volume flow (BF) was calculated as the product of TAMV and CSA (BF = TAMV✕CSA). Data are presented as mean (SD) and analyzed with a 2(time) by 3(site) repeated measures ANOVA and follow-up paired t-tests. Results: Participants (N=7; 5 males) demographics are as follows: age: 25(7) years; height: 179(7) cm; BMI: 25.0 (3.4) kg/m2; body fat: 19 (7) %. There was no interaction [F(2,17)=0.56, p=.58] but were significant main effects for both time [F(1,17)=14.05, p=.002] and site [F(2,17)=33.99, p<.001]. During HNP, popliteal BF increased by 41% [3.4(1.9) to 4.8(2.6) ml/min, p=.008] with a 12% increase [0.36(.15) to 0.41(.16) cm 2 , p=.009] in CSA and 22% increase [9.4(4.5) to 11.5(4.3) cm/s, p=.015] in TAMV; brachial BF increased by 24% [3.1(1.2) to 3.9(1.3), p=.007] with a 4% increase [0.20(0.04) to 0.21(0.04) cm 2 , p=.008] in CSA and 19% increase [15.4(4.9) to 18.3(5.0) cm/s, p=.008] in TAMV; and carotid BF increased by 14% [11.8(3.1) to 13.4(3.1) ml/min, p=.11] with a 6% increase [0.37(.06) to 0.39(0.08) cm 2 , p=.14] in CSA and 8% increase [32.6(10.2) to 35.4(11.1) cm/s, p=.13] in TAMV. Percent changes in BF, CSA, and TAMV were often greater at the popliteal than the brachial (p=.14; p=.069; p=.57) and carotid (p=.11; p=.11; p=.18) arteries with smaller differences between brachial and carotid arteries (p=.56; p=.33; p=.25). Conclusions: HNP applied to the feet and calves increased BF in the popliteal, brachial, and carotid arteries through changes in both TAMV and CSA. Increases in BF were greatest at the popliteal artery. Whether increases in blood flow are a result of increased cardiac output or at the expense of blood flow elsewhere is unknown. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In Vitro Digestive Analysis of Digestible and Resistant Starch Fractions, with Concurrent Glycemic Index Determination, in Whole Grain Wheat Products Minimally Processed for Reduced Glycaemic Impact

Eight wheat products differing in texture (porridge vs. bread), grain fineness (fine, kibbled, intact), and cooking (raw vs. cooked), with pre-measured glycaemic indexes (GI), were analysed by in vitro amylolytic digestion to determine effects of processing to reduce GI on quantities of starch fractions differing in digestibility. The accuracy and precision of the in vitro analysis was assessed from its ability to concurrently predict clinical GI. In porridges, kernel intactness and lack of cooking reduced GI while increasing Type 1 (inaccessible) and Type 2 (ungelatinised) resistant starch. Porridge in vitro GI values (GIiv), calculated from the area under in vitro digestion curves minus estimated blood glucose disposal, were: raw fine, 26.3; raw kibbled, 12.6; cooked fine, 63.9; cooked kibbled, 44.1; and correlated closely with clinical GI values (R2 = 0.97). In bread, the negative association of kernel intactness and resistant starch with GI was seen in vitro but not in vivo. Bread GIiv values were: roller milled flour, 67.4; stoneground flour 61.1; kibbled grain, 53.0; kibbled + intact kernel, 49.5; but correlation with clinical values was low (R2 = 0.47), and variability in the clinical results was high (clinical CV = 72.5%, in vitro CV = 3.7%). Low glycaemic potency of wheat by minimal processing was achieved by maintaining particle size, avoiding hydrothermal treatment, avoiding crushing and using a food matrix requiring little chewing for ingestion. Use of in vitro digestive analysis for high precision measurement of starch fractions with potential secondary health benefits was validated by accurate concurrent prediction of the glycaemic index but needed to account for effects of chewing.

Gastric inhibitory polypeptide as the new candidate for the interaction of skeletal muscle blood flow and glucose disposal.

Gastric inhibitory polypeptide as the new candidate for the interaction of skeletal muscle blood flow and glucose disposal.

SAHA induces white fat browning and rectifies metabolic dysfunctions via activation of ZFPs.

Several histone deacetylase (HDAC) inhibitors have been shown to play beneficial roles in treating obesity and its related metabolic syndromes. However, the underlying mechanisms are still not understood well. In this study, we examined the potential roles of SAHA, a potent inhibitor of HDACs, on energy expenditure and explored the molecular mechanism involved. Our data showed that SAHA induces less lipid accumulation and smaller lipid droplets in cultured adipocytes. In vivo studies showing SAHA reduces body weight gain and increases core temperature in lean and obese mice. Furthermore, SAHA accelerates blood glucose disposal, improves insulin sensitivity and attenuates fatty liver in obese animals. Transcriptome sequencing found that a group of zinc finger proteins (Zfps) was up-regulated by SAHA. Functional studies showed that the knockdown of Zfp691 or Zfp719 largely abolishes SAHA-induced Ucp1 expression in adipocytes. ChIP assay showed that SAHA stimulates histone H3 acetylation at Zfp719 promoter. Luciferase reporter analysis revealed that Zfp719 activates Ucp1 promoter. As a consequence, forced expression of Zfp719 increases Ucp1 expression and promotes lipid catabolism in adipocytes. Taken together, our data indicate that by stimulating axis of ZFPs-UCP1, SAHA induces white fat browning and energy consumption, which makes it a potential drug for treating obesity and related metabolic dysfunctions.

The Precious Few Grams of Glucose During Exercise.

As exercise intensity exceeds 65% of maximal oxygen uptake carbohydrate energy sources predominate. However, relative to the meager 4–5 g blood glucose pool size in a postabsorptive individual (0.9–1.0 g·L−1 × 5 L blood = 18–20 kcal), carbohydrate (CHO) oxidation rates of 20 kcal·min−1 can be sustained in a healthy and fit person for one hour, if not longer, all the while euglycemia is maintained. While glucose rate of appearance (i.e., production, Ra) from splanchnic sources in a postabsorptive person can rise 2–3 fold during exercise, working muscle and adipose tissue glucose uptake must be restricted while other energy substrates such as glycogen, lactate, and fatty acids are mobilized and utilized. If not for the use of alternative energy substrates hypoglycemia would occur in less than a minute during hard exercise because blood glucose disposal rate (Rd) could easily exceed glucose production (Ra) from hepatic glycogenolysis and gluconeogenesis. The goal of this paper is to present and discuss the integration of physiological, neuroendocrine, circulatory, and biochemical mechanisms necessary for maintenance of euglycemia during sustained hard physical exercise.

Study of the chemical compatibility of two active substances and stability of their solution

The metabolic field aiming at theoretical and applied analysis of metabolic processes of different levels to be the basis or the background of many diseases has been actively developing for the last decade. Especially, the concepts of the role of the cell energy metabolic imbalance during various pathologic processes that are based, first of all, on the mitochondrial deficiency have been actively developed.The irreversible cell damage when affected by the disturbing agents occurs from the moment of damage of organelles- the ATP generating cell systems. The paper studies the opportunity of creating the combined dosage formulation containing two active pharmaceutical ingredients (succinic acid and butafosfan) based on their chemical compatibility. The literature contains no information concerning the use of butafosfan and succinic acid in the same dosage formulation. Butafosfan improves the blood glucose disposal that stimulates the energy metabolism and accelerates metabolic processes due to the ADP-ATP cycle stimulation. Succinic acid can directly improve the energy-synthesizing function of mitochondria by increasing the succinate delivery and consumption by ischemic cells, participate in implementation of the succinic acid quick oxidation by succinate dehydrogenase, as well as activation of the mitochondrial respiratory chain leading to the ATP quick resynthesis. One of the obligatory phases of research is identification and study of physical and chemical properties of the active ingredient, compatibility assessment of the active ingredient and excipients, and in case of combination drugs - also compatibility assessment of ingredients themselves. To choose the necessary conditions during the solution technology development, the chemical properties, stability and compatibility of these pharmaceutical substances were studied.

Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice

Although epidemiological data and results from rodent studies support an inverse relationship between nicotine consumption and body weight, the molecular mechanisms are poorly understood. CD-1 mice were fed a basal diet or a basal diet containing low or high dose smokeless tobacco blend or high dose nicotine tartrate for 14 weeks. High dose tobacco blend and nicotine tartrate diets vs. basal diet reduced mouse body weight (16.3% and 19.7%, respectively), epididymal (67.6% and 72.5%, respectively) and brown adipose weight (42% and 38%, respectively), epididymal adipocyte size (46.4% and 41.4%, respectively), and brown adipose tissue lipid droplet abundance, with no elevation of adipose tissue inflammation. High dose tobacco blend and nicotine diets also increased mouse physical activity and decreased respiratory exchange ratio, suggesting that high dose nicotine intake induces adipose tissue triglyceride lipolysis to provide fatty acids as an energy source. Both low and high dose tobacco blend and nicotine diet feeding vs. basal diet increased plasma insulin levels (2.9, 3.6 and 4.3-fold, respectively) and improved blood glucose disposal without affecting insulin sensitivity. Feeding of the high dose tobacco blend or nicotine feeding in mice induces body weight loss likely by increasing physical activity and stimulating adipose tissue triglyceride lipolysis.

Species-specific effects of neuregulin-1β (cimaglermin alfa) on glucose handling in animal models and humans with heart failure

Neuregulin-1β is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs. Since acute hypoglycemia could be a safety concern, blood glucose changes in the above pig study were further investigated. In addition, basal glucose and glucose disposal were investigated in mice. Finally, as part of standard clinical chemistry profiling in a single ascending-dose human safety study, blood glucose levels were evaluated in patients with heart failure after cimaglermin alfa treatment. A single intravenous injection of cimaglermin alfa at doses of 0.8mg/kg and 2.6mg/kg in mice resulted in a transient reduction of blood glucose concentrations of approximately 20% and 34%, respectively, at 2h after the treatment compared to pre-treatment levels. Similar results were observed in diabetic mice. Treatment with cimaglermin alfa also increased blood glucose disposal following oral challenge in mice. However, no significant alterations in blood glucose concentrations were found in human heart failure patients at 0.5 and 2h after treatment with cimaglermin alfa over an equivalent human dose range, based on body surface area. Taken together, these data indicate strong species differences in blood glucose handling after cimaglermin alfa treatment, and particularly do not indicate that this phenomenon should affect human subjects.

Dapagliflozin suppresses glucagon signaling in rodent models of diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose. In these type 1 diabetic rats, glucose stimulated glucagon secretion by alpha cells; this was prevented by dapagliflozin. Two models of type 2 diabetes, severely diabetic Zucker rats and db/db mice fed dapagliflozin, showed significant improvement of blood glucose levels and glucose disposal, with reduced evidence of glucagon signaling in the liver, as exemplified by reduced phosphorylation of hepatic cAMP-responsive element binding protein, reduced expression of phosphoenolpyruvate carboxykinase 2, increased hepatic glycogen, and reduced hepatic glucose production. Plasma glucagon levels did not change significantly. However, dapagliflozin treatment reduced the expression of the liver glucagon receptor. Dapagliflozin in rodents appears to lower blood glucose levels in part by suppressing hepatic glucagon signaling through down-regulation of the hepatic glucagon receptor.

Implications of Palmitoleic Acid (Palmitoleate) On Glucose Homeostasis, Insulin Resistance and Diabetes.

Obesity is a metabolic, multifactorial disease that is underpinned by factors such as genetics, epigenetics, as well as high-energy food intake and sedentarism. Obesity is often associated with, and exacerbated by, other metabolic disorders such as type 2 diabetes mellitus (T2DM). A hallmark of T2DM is failure of insulin secretion from pancreatic β-cell to regulate blood glucose disposal into peripheral tissues, such as skeletal muscle, termed insulin resistance, as well as deregulation of pancreatic α-cell function. It has been proposed that insulin resistance is, in part, a consequence of impaired signal transduction of insulin caused by several molecules released from adipose tissue that include (adipo)cytokines and fatty acids. However, not all fatty acids exert a negative impact on insulin sensitivity. In fact, it has been suggested that palmitoleic acid (16:1n-7) has hormone-like properties and improves some metabolic parameters that are impaired in obesity and T2DM. Moreover, in vitro approaches reveal that cis-16:1n-7 can influence pancreatic β-cell survival, insulin secretion, and skeletal muscle insulin response and adipocyte metabolism. In vivo experiments using animal models show that the ingestion of cis-16:1n-7 or sources of it (e.g., macadamia oil) can partially prevent the metabolic alterations caused by high-fat/carbohydrate diets. In general, studies in humans found positive associations between higher trans-16:1n-7 proportion in plasma phospholipids and improved insulin sensitivity or decreased the onset of T2DM. However, plasma cis-16:1n-7 data are still controversial. In this brief review, we discuss the main studies on 16:1n-7 effects on obesity and T2DM and their potential for clinical application.

Digestive analysis of processing effects on the glycaemic impact of oats in vitro

Forty six lines of oats from a program of breeding for low glycaemic impact were assessed by in vitro digestive analysis that allowed for theoretical effects of homeostasis on blood glucose concentrations. The oats were steamed and rolled (“rolled oats”; RO), and a portion made into porridge (PO) before in vitro digestive analysis. Carbohydrate digestibility was much greater and more rapid for PO than RO after 20 min digestion (RO, 16.9 g/100 g; PO, 42.5 g/100g on a dry oats basis) but similar after 120 min digestion (43 g versus49.8 g), reflecting a high proportion of slowly digested starch in RO. Taking into account theoretical blood glucose disposal, RO was equivalent in glycaemic effect to 10.8 g of glucose and the PO to 17.5 g of glucose per 40 g serving (10.8 versus 17.5 g glucose equivalents). Based on published GI values, in vitro glycaemic analysis allowing for homeostasis provided realistic relative estimates of effects of processing on glycaemic properties of cereal foods.

One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.

Using mice rendered insulin resistant with high fat diets (HFD), we examined blood glucose levels and insulin resistance after i.v. delivery of an adeno-associated virus type 8 encoding murine urocortin 2 (AAV8.UCn2). A single i.v. injection of AAV8.UCn2-normalized blood glucose and glucose disposal within weeks, an effect that lasted for months. Hyperinsulinemic-euglycemic clamps showed reduced plasma insulin, increased glucose disposal rates, and increased insulin sensitivity following UCn2 gene transfer. Mice with corticotropin-releasing hormone type 2-receptor deletion that were rendered insulin resistant by HFD showed no improvement in glucose disposal after UCn2 gene transfer, indicating that the effect requires UCn2's cognate receptor. We also demonstrated increased glucose disposal after UCn2 gene transfer in db/db mice, a second model of insulin resistance. UCn2 gene transfer reduced fatty infiltration of the liver in both models of insulin resistance. UCn2 increases Glut4 translocation to the plasma membrane in skeletal myotubes in a manner quantitatively similar to insulin, indicating a mechanism through which UCn2 operates to increase insulin sensitivity. UCn2 gene transfer, in a dose-dependent manner, is insulin sensitizing and effective for months after a single injection. These findings suggest a potential long-term therapy for clinical type-2 diabetes.

Differential effects of early-life NMDA receptor antagonism on aspartame-impaired insulin tolerance and behavior

We have previously showed that lifetime exposure to aspartame, commencing in utero via the mother's diet, may impair insulin tolerance and cause behavioral deficits in adulthood via mechanisms which are incompletely understood. The role of the CNS in regulating glucose homeostasis has been highlighted by recent delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors (NMDARs) are important in maintaining glucose homeostasis, in addition to regulating certain aspects of behavior. Since the gut-brain axis can be modulated by fetal programming, we hypothesized that early-life NMDAR antagonism may affect aspartame-induced glucose deregulation in adulthood, and may alter the aspartame behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to aspartame commencing in utero, in the presence and absence of maternal administration of the competitive NMDAR antagonist CGP 39551, from conception until weaning. Drug/diet interactions in adulthood glucocentric and behavioral parameters were assessed. Aspartame exposure elevated blood glucose and impaired insulin-induced glucose disposal during an insulin tolerance test, which could be normalized by NMDAR antagonism. The same effects were not observed in control diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of adult offspring indicated that NMDAR antagonism of control diet mice caused hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, reduced exploratory activity and increased anxiety-related behavior were apparent in aspartame diet mice with early-life NMDAR antagonism. Conclusion: significant drug/diet interactions in glucocentric and behavioral parameters were identified in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a possible involvement of early NMDAR interactions in aspartame-impaired glucose homeostasis and behavioral deficits.

Seasonal Cold Exposure Modulates Metabolic Phenotype and Mitochondrial Function in Obese Golden‐Mantled Ground Squirrels

Golden‐mantled ground squirrels (Callospermophilus lateralis; GMGS) develop seasonal obesity in early autumn, which provides essential fuel stores for successful hibernation through the long Rocky Mountain winter. This is facilitated by circannual variations in hormones regulating food intake and metabolism independent of environmental cues, but is accompanied by a decrease in ambient temperature that might also influence metabolic phenotype. The present study evaluated the effect of seasonal cold exposure on body composition, glucose tolerance and tissue mitochondrial function in obese GMGS prior to hibernation. We hypothesized that cold exposure compliments seasonal adiposity by altering metabolic and mitochondrial parameters that further optimize physiological preparation for hibernation. Adult GMGS were captured in mid‐summer and transferred to an animal facility maintained at 22 deg C, and provided standard rodent chow (Harlan 2918) and water ad libitum. Animals were allowed to acclimate to the new environment for at least 4 weeks before being sacrificed for baseline evaluation as lean summer controls (Lean; N = 7) or randomized to continue on the ab libitum diet for 4–6 more weeks at 22 deg C (Ob‐warm; N = 4) or 15 deg C to simulate the seasonal decrease in temperature normally encountered by animals in the wild (Ob‐cold; N = 6). Lean animals had lower body weight (247 ± 12 g) and body fat (25 ± 4 %) compared to obese groups, with no difference between Ob‐warm (312 ± 16 g; 47 ± 2 % fat) and Ob‐cold (302 ± 23 g; 47 ± 5 % fat). Blood glucose disposal following a 2 g/kg i.p. glucose challenge was much more rapid in Lean compared to Ob groups, and greater in Ob‐cold vs. Ob‐warm animals, indicating an expected decrease in glucose tolerance with obesity that was attenuated by cold exposure. Liver mitochondria from obese animals exhibited greater maximal ADP‐dependent (OXPHOS) respiration vs. Lean with both carbohydrate (pyruvate) and lipid (palmitoylcarnitine) substrates. Cold exposure attenuated the increase in lipid OXPHOS in obese animals, but had no effects on carbohydrate OXPHOS capacity. Conversely, in cardiac mitochondria, maximal and carbohydrate OXPHOS capacity was similar between Lean and Ob‐warm groups, but significantly elevated in Ob‐cold animals. In muscle mitochondria, obesity reduced carbohydrate OXPHOS capacity, with no significant effects on lipid OXPHOS and no modulation by cold exposure. Taken together, these data suggest that seasonal cold exposure modifies metabolic responses to obesity in pre‐hibernating GMGSs, leading to improvements in systemic glucose disposal, tissue‐specific alterations in mitochondrial substrate utilization, and enhancement of cardiac mitochondrial OXPHOS capacity. These adaptations might serve to optimize systemic preparation for prolonged hypometabolism and reliance on lipid stores during hibernation, and provide insight into the metabolic effects of physiologic cold exposure with potential relevance to obesity‐related metabolic disorders.Support or Funding InformationFunding for this work was provided in part by grants from the USDA and American Heart Association to AJC.

Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose. Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using exvivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1-5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging. In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased. The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.

Impact of taurine depletion on glucose control and insulin secretion in mice

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism.

Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice.

Impairment of insulin signaling in skeletal muscle detrimentally affects insulin-stimulated disposal of glucose. Restoration of insulin signaling in skeletal muscle is important as muscle is one of the major sites for disposal of blood glucose. Recently, unacylated ghrelin (UnAG) has received attention in diabetic research due to its favorable actions on improving glucose tolerance, glycemic control, and insulin sensitivity. The investigation of UnAG has entered phase Ib clinical trial in type 2 diabetes and phase II clinical trial in hyperphagia in Prader-Willi syndrome. Nonetheless, the precise mechanisms responsible for the anti-diabetic actions of UnAG remain incompletely understood. In this study, we examined the effects of UnAG on restoring the impaired insulin signaling in skeletal muscle of db/db diabetic mice. Our results demonstrated that UnAG effectively restored the impaired insulin signaling in diabetic muscle. UnAG decreased insulin receptor substrate (IRS) phosphorylation, increased protein kinase B (Akt) phosphorylation, and, hence, suppressed mTOR signaling. Consequently, UnAG enhanced Glut4 localization and increased PDH activity in the diabetic skeletal muscle. Intriguingly, our data indicated that UnAG normalized the suppressed autophagic signaling in diabetic muscle. In conclusion, our findings illustrated that UnAG restored the impaired insulin and autophagic signaling in skeletal muscle of diabetic mice, which are valuable to understand the underlying mechanisms of the anti-diabetic action of UnAG at peripheral skeletal muscle level.

In-vivo measurement of muscle tension: dynamic properties of the MC sensor during isometric muscle contraction.

Skeletal muscle is the largest tissue structure in our body and plays an essential role for producing motion through integrated action with bones, tendons, ligaments and joints, for stabilizing body position, for generation of heat through cell respiration and for blood glucose disposal. A key function of skeletal muscle is force generation. Non-invasive and selective measurement of muscle contraction force in the field and in clinical settings has always been challenging. The aim of our work has been to develop a sensor that can overcome these difficulties and therefore enable measurement of muscle force during different contraction conditions. In this study, we tested the mechanical properties of a “Muscle Contraction” (MC) sensor during isometric muscle contraction in different length/tension conditions. The MC sensor is attached so that it indents the skin overlying a muscle group and detects varying degrees of tension during muscular contraction. We compared MC sensor readings over the biceps brachii (BB) muscle to dynamometric measurements of force of elbow flexion, together with recordings of surface EMG signal of BB during isometric contractions at 15° and 90° of elbow flexion. Statistical correlation between MC signal and force was very high at 15° (r = 0.976) and 90° (r = 0.966) across the complete time domain. Normalized SD or σN = σ/max(FMC) was used as a measure of linearity of MC signal and elbow flexion force in dynamic conditions. The average was 8.24% for an elbow angle of 90° and 10.01% for an elbow of angle 15°, which indicates high linearity and good dynamic properties of MC sensor signal when compared to elbow flexion force. The next step of testing MC sensor potential will be to measure tension of muscle-tendon complex in conditions when length and tension change simultaneously during human motion.

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action.

The effect of post-exercise caffeine and chlorogenic acid supplementation on blood glucose disposal and insulin sensitivity

Background Caffeine and chlorogenic acid are two compounds in green coffee beans that alter blood glucose disposal and insulin sensitivity. Caffeine has been shown to decrease glucose disposal and insulin sensitivity when taken 60 minutes prior to an oral glucose tolerance test in humans, whereas chlorogenic acid has been shown to increase glucose disposal and insulin sensitivity in humans. The purpose of this study was to investigate the effect of ingesting caffeine with dextrose or chlorogenic acid with dextrose immediately after an exhaustive bout of cycling on blood glucose and insulin disposal when compared to ingesting dextrose alone. Methods