Clearance Rate Of Glucose Research Articles

Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.

Compared with some other species, insulin dysregulation in equids is poorly understood. However, hyperinsulinemia causes laminitis, a significant and often lethal disease affecting the pedal bone/hoof wall attachment site. Until recently, hyperinsulinemia has been considered a counterregulatory response to insulin resistance (IR), but there is growing evidence to support a gastrointestinal etiology. Incretin hormones released from the proximal intestine, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, augment insulin secretion in several species but require investigation in horses. This study investigated peripheral and gut-derived factors impacting insulin secretion by comparing the response to intravenous (iv) and oral d-glucose. Oral and iv tests were performed in 22 ponies previously shown to be insulin dysregulated, of which only 15 were classified as IR (iv test). In a more detailed study, nine different ponies received four treatments: d-glucose orally, d-glucose iv, oats, and commercial grain mix. Insulin, glucose, and incretin concentrations were measured before and after each treatment. All nine ponies showed similar iv responses, but five were markedly hyperresponsive to oral d-glucose and four were not. Insulin responsiveness to oral d-glucose was strongly associated with blood glucose concentrations and oral glucose bioavailability, presumably driven by glucose absorption/distribution, as there was no difference in glucose clearance rates. Insulin was also positively associated with the active amide of GLP-1 following d-glucose and grain. This study has confirmed a functional enteroinsular axis in ponies that likely contributes to insulin dysregulation that may predispose them to laminitis. Moreover, iv tests for IR are not reliable predictors of the oral response to dietary nonstructural carbohydrate.

Intramyocellular lipid content in subjects with impaired fasting glucose after telmisartan treatment, a randomised cross-over trial

Ectopic lipid accumulation in skeletal muscle is associated with insulin resistance. Telmisartan improves metabolic parameters in type 2 diabetic patients. The aim of our study was to evaluate the in vivo effect of telmisartan on intramyocellular lipid content (IMCL) in subjects with impaired fasting glucose (IFG) by magnetic resonance spectroscopy (MRS). We enrolled 10 subjects with IFG in a cross-over, placebo-controlled, randomized, double-blind trial, treated with 3 weeks of telmisartan (160 mg daily) or placebo. After completing each treatment, a hyperinsulinaemic euglycaemic clamp (1 mU/kg per min; 5 mmol/l; 120 min) to assess insulin action (metabolic clearance rate of glucose, MCR) and 1H MRS of the m. tibialis anterior using a MR Scanner Siemens Vision operating at 1.5 T to evaluate IMCL content, were performed. Plasma adipokine levels were determined simultaneously. Telmisartan treatment resulted in a lower fasting plasma glucose (FPG) (p < 0.05), but insulin action was comparable to after placebo. Telmisartan did not affect IMCL content. After placebo, IMCL correlated negatively with total cholesterol (p < 0.001), MCR (p < 0.05) and adiponectin (p < 0.05) and positively with FPG (p < 0.05). After telmisartan treatment there was only a positive correlation between IMCL and TNFα (p < 0.05). IMCL content is related to parameters of glucose metabolism and insulin action in sedentary IFG subjects. A short telmisartan treatment did not affect the IMCL content despite its positive effect on FPG. The improvement in FPG was probably mediated through interference with other metabolic pathways.

Characterization of the intravenous glucose tolerance test and the combined glucose–insulin test in donkeys

Glucose–insulin dynamic challenges such as the intravenous glucose tolerance test (IVGTT) and combined glucose–insulin test (CGIT) have not been described in donkeys. The objectives of this study were (1) to characterize the IVGTT and CGIT in healthy adult donkeys, and (2) to establish normal glucose–insulin proxies. Sixteen donkeys were used and body morphometric variables obtained each. For the IVGTT, glucose (300 mg/kg) was given IV. For the CGIT, glucose (150 mg/kg) followed by recombinant insulin (0.1 IU/kg) were administered IV. Blood samples for glucose and insulin determinations were collected over 300 min.In the IVGTT the positive phase lasted 160.9 ± 13.3 min, glucose concentration peaked at 323.1 ± 9.2 mg/dL and declined at a rate of 1.28 ± 0.15 mg/dL/min. The glucose area under the curve (AUC) was 21.4 ± 1.9 × 103 mg/dL/min and the insulin AUC was 7.2 ± 0.9 × 103 µIU/mL/min. The positive phase of the CGIT curve lasted 44 ± 3 min, with a glucose clearance rate of 2.01 ± 0.18 mg/dL/min. The negative phase lasted 255.9 ± 3 min, decreasing glucose concentration at rate of −0.63 ± 0.06 mg/dL/min, and reaching a nadir (33.1 ± 3.6 mg/dL) at 118.3 ± 6.3 min. The glucose and insulin AUC values were 15.2 ± 0.9 × 103 mg/dL/min and 13.2 ± 0.9 × 103 µIU/mL/min. This is the first study characterizing CGIT and IVGTT, and glucose–insulin proxies in healthy adult donkeys. Distinct glucose dynamics, when compared with horses, support the use of species-specific protocols to assess endocrine function.

Diets rich in starch improve the efficiency of amino acids use by the mammary gland in lactating Jersey cows

The objective of this study was to test whether the greater milk N yield usually observed when feeding diets based on starch versus fiber was the consequence of a higher efficiency of AA use across the mammary gland and whether this effect depended on dietary crude protein (CP) content. Five midlactation multicatheterized Jersey cows were fed 4 isoenergetic diets to provide 2 different carbohydrate compositions (CHO; rich in starch vs. rich in fiber) crossed by 2 different protein levels (12.0 vs. 16.5% CP) and according to a 4×4 Latin square design. Blood samples were collected at the end of each treatment period from the mesenteric artery and mammary vein to determine mammary net nutrient fluxes. The nature of nutrients taken up by the mammary gland differed between starch and fiber diets: mammary net uptake of acetate increased with fiber versus starch diets, whereas mammary net uptake and clearance rate of glucose increased with starch versus fiber diets but only at a normal CP level. In addition, the mammary net uptake of total, essential, and branched-chain AA (BCAA) was significantly enhanced (12, 11, and 26% on average, respectively) when feeding starch versus fiber diets, in line with a greater milk protein yield (7% on average) and regardless of the CP level. The conversion efficiency of plasma essential AA into milk protein was improved with starch diets (33.7% on average) compared with fiber diets (27.5% on average). This higher mammary efficiency use of AA with starch diets was accompanied by a greater fractional extraction and clearance rate of AA belonging to group 2 (BCAA, Lys, Thr) by the mammary gland in absence of effects of CHO on either the mammary blood flow or the mammary AA metabolism. The positive effect of starch diets on mammary clearance rate and uptake of BCAA observed in this study was further improved when increasing dietary CP from 12.0 to 16.5%. Concerning the individual AA, Leu was the only whose mammary uptake accounted for a higher proportion of total essential AA in diets based on starch versus fiber and whose mammary uptake to milk output ratio was modified (together with Pro). Diets rich in starch versus fiber improved the mammary AA utilization; however, some CHO × CP interactions on mammary metabolism support the concept of different metabolic pathways by which starch diets improve milk protein yield at the 2 studied CP levels. Results from this study suggest that mammary Leu and glucose metabolism can be modulated by the supply of glucogenic nutrients to the mammary gland.

Relationships among Body Condition, Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression during the Grazing Season in Mares

Obesity and insulin resistance have been shown to be risk factors for laminitis in horses. The objective of the study was to determine the effect of changes in body condition during the grazing season on insulin resistance and the expression of genes associated with obesity and insulin resistance in subcutaneous adipose tissue (SAT). Sixteen Finnhorse mares were grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland (NG) from the end of May to the beginning of September. Body measurements, intravenous glucose tolerance test (IVGTT), and neck and tailhead SAT gene expressions were measured in May and September. At the end of grazing, CG had higher median body condition score (7 vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05) and body weight (618 kg vs. 572 kg ± 10.21 (mean ± SEM); P=0.02), and larger waist circumference (P=0.03) than NG. Neck fat thickness was not different between treatments. However, tailhead fat thickness was smaller in CG compared to NG in May (P=0.04), but this difference disappeared in September. Greater basal and peak insulin concentrations, and faster glucose clearance rate (P=0.03) during IVGTT were observed in CG compared to NG in September. A greater decrease in plasma non-esterified fatty acids during IVGTT (P<0.05) was noticed in CG compared to NG after grazing. There was down-regulation of insulin receptor, retinol binding protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of adiponectin (ADIPOQ), adiponectin receptor 1 and stearoyl-CoA desaturase (SCD) gene expressions in SAT of both groups during the grazing season (P<0.05). Positive correlations were observed between ADIPOQ and its receptors and between SCD and ADIPOQ in SAT (P<0.01). In conclusion, grazing on CG had a moderate effect on responses during IVGTT, but did not trigger insulin resistance. Significant temporal differences in gene expression profiles were observed during the grazing season.

Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits

The administration of statin might increase the risk of new-onset diabetes in hypercholesterolemic patients based on the recent clinical evidence. However, the causal relationship must be clarified and confirmed in animal experiments. Therefore, we mimicked hypercholesterolemia by feeding rabbits a high-cholesterol diet (HCD) and performed 16 weeks of atorvastatin administration to investigate the effect of statin on glucose metabolism. The intravenous glucose tolerance test showed that plasma glucose levels in the statin-treated rabbits were consistently higher and that there was a slower rate of glucose clearance from the blood than in HCD rabbits. The incremental area under the curve for glucose in the statin-treated rabbits was also significantly larger than in the HCD rabbits. However, there was no significant difference between the two groups in the intravenous insulin tolerance test. The glucose-lowering ability of exogenous insulin was not impaired by statin treatment in hypercholesterolemic rabbits. The administration of a single dose of statin did not affect glucose metabolism in normal rabbits. The statin also significantly increased the levels of high-density lipoprotein cholesterol, alanine aminotransferase and aspartate transaminase and decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the hypercholesterolemic rabbits, whereas it did not affect plasma levels of glucose and insulin. The current results showed that atorvastatin treatment resulted in a significant delay of glucose clearance in hypercholesterolemic rabbits, and this rabbit model could be suitable for studying the effects of statin on glucose metabolism.

Difference in Postprandial GLP‐1 Response Despite Similar Glucose Kinetics after Consumption of Wheat Breads with Different Particle Size in Healthy Men

Consumption of low glycemic index (GI) foods has been associated with beneficial health effects. Underlying mechanisms are not yet fully elucidated.We aimed to investigate the differences in postprandial glucose kinetics and metabolic response after consumption of a high and a low GI fiber‐rich wheat bread, obtained by varying wheat particle size.In a randomized crossover study ten healthy male volunteers consumed 13C‐enriched wheat breads with different structures; a control bread (CB) made from wheat flour combined with wheat bran, and a kernel bread (KB) in which 85% of the flour was substituted with broken wheat kernels. The use of a dual isotope technique enabled calculation of in vivo glucose kinetics: rate of appearance of exogenous glucose, endogenous glucose production, and glucose clearance rate. In addition, postprandial plasma concentrations of glucose, insulin, glucagon and incretins were analyzed.Despite the attempt to create a low GI bread by the substitution of flour by broken kernels, the glycemic response and the glucose kinetics were quite similar after consumption of CB and KB. Interestingly, the incretin glucagon‐like peptide‐1 (GLP‐1) response was much lower after KB compared to CB (iAUC, P &lt; 0.005).Thus, substitution of 85% wheat flour by broken kernels in bread did not result in a difference in glucose response and kinetics, but in a pronounced difference in GLP‐1 response. Changing the processing conditions of wheat for baking bread can influence the metabolic response beyond glycemia.

Clinical Biopotency of Insulin Analogues: Comparative Assessment in Different Species

ObjectiveThe clinical potency of human insulin has classically been evaluated following the U.S. Pharmacopeia (USP) guideline for comparison to an international standard (IS) of activity (IU). However, since insulin analogues cannot be standardized against IS, there is a need for a bioassay to assess clinical specific activity (U). To this extent, we compared the biopotency (U) of different insulin products in different species and used human (recombinant) and pork (natural) insulin as reference standards.Methods: New Zealand White rabbits were fasted and injected subcutaneously (s.c.) at a dose level of 0.5 U/kg. Diabetic Yucatan miniature swine (Sus scrofa) were injected s.c. at dose level of 0.1 U/kg. Normal insulin suppression tests (nIST) were conducted in primates (Macaca fascicularis) receiving a bolus intravenous (i.v.) infusion of glucose. Insulin products were given at dose level of 0.05 U/kg. Glucose levels were recorded using handheld glucometer devices. The blood glucose kinetic (BGPK), the blood glucose area under the curve (BGAUC) and the slope of the blood glucose clearance rate (kG) were used to assess clinical biopotency.Results: The BGPK for short‐acting human and pork insulin were similar in the rabbit assay but their respective BGAUCs were different (ratio of 1.2). Accordingly pork insulin was more potent during nIST in the non‐human primate (slope of ‐0.012 vs. ‐0.010; pork and human, respectively).ConclusionOur data indicate that the clinical biopotency of insulin products can be assessed using BGAUC and kG, but that only the type 1 diabetic miniature swine can discriminate between differences in clinical biopotency for all aspects of BGPK.

Potential capacity of Senegalese sole (Solea senegalensis) to use carbohydrates: Metabolic responses to hypo- and hyper-glycaemia

Abstract Glucose tolerance in fish is species-dependent and closely related to feeding habits. The capacity of each species to regulate glucose homeostasis is indicative of its potential to utilize dietary carbohydrates (CH). Senegalese sole is a carnivorous species but its nutrient requirements are still under debate. In the present study, we aimed to evaluate the capacity of Senegalese sole (20 ± 4 g) reared at 20 °C to cope with marked changes in circulating levels of glucose through assessment of glucose tolerance by an oral glucose tolerance test and metabolic responses after induction of hyper-glycaemic and hypo-glycaemic conditions by intraperitoneal injections of D-glucose (600 mg kg −X1 body mass) or insulin (5 mg kg −1 body mass), respectively. Changes observed in the levels of metabolites and enzyme activities at hepatic level show a metabolic response to counter-regulate acute changes in circulating glucose levels. Thus, glycogen levels in liver decreased markedly in hypo-glycaemic fish (16-fold change) and increased in hyper-glycaemic fish (1.3-fold change) compared with normo-glycaemic fish 24 h after treatment. Furthermore, activities of G6Pase (involved in gluconeogenesis) and GPase (involved in glycogenolysis) were higher in hypo- than in hyper-glycaemic fish after 24 h of treatment (2.9-fold change for G6Pase and 7.1-fold change for GPase). The present results indicate that Senegalese sole has a fast plasma clearance rate of glucose compared with other carnivorous fish species and show a good capacity to deal with different glycaemic conditions by undertaking metabolic changes able to restore glucose homeostasis. These results suggest that Senegalese sole may be able to use dietary CH efficiently, allowing the incorporation of more sustainable and cheaper energy sources in aquafeeds for this species.

The structure of wheat bread influences the postprandial metabolic response in healthy men.

Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.

Effects of Cr Methionine on Glucose Metabolism, Plasma Metabolites, Meat Lipid Peroxidation, and Tissue Chromium in Mahabadi Goat Kids

This study was designed to investigate the effects of chromium methionine (Cr-Met) on glucose metabolism, blood metabolites, meat lipid peroxidation, and tissue chromium (Cr) in Mahabadi goat kids. Thirty-two male kids (16.5 ± 2.8 kg BW, 4-5 months of age) were fed for 90 days in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 0.5, 1, and 1.5 mg Cr as Cr-Met/animal/daily. Blood samples were collected via heparin tubes from the jugular vein on 0, 21, 42, 63, and 90 days of experiment. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. At the end of the feeding trial, the kids were slaughtered, and the liver, kidney, and longissimus dorsi (LD) muscle samples were collected. Plasma glucose, insulin, and triglyceride concentrations were decreased by Cr supplementation (P < 0.05). LD muscle malondialdehyde (MDA) decreased, and plasma and tissue Cr contents increased with increasing supplemental Cr levels (P < 0.05). Plasma glucose concentrations at 30 and 60 min after glucose infusion were lower in the kids fed 1.5 mg Cr diet than the kids fed control diet (P < 0.05). The IVGTT indicated that the kids supplemented with 1.5 mg Cr had higher glucose clearance rate (K) and lower glucose half-life (T½; P < 0.05). Glucose area under the response curve (AUC) from 0 to 180 min after glucose infusion was decreased linearly (P < 0.01) by supplemental Cr. The results suggested that supplemental Cr may improve glucose utilization and lipid oxidation of meat in fattening kid.

Mathematical modeling of the insulin signal transduction pathway for prediction of insulin sensitivity from expression data

Mathematical models of biological pathways facilitate a systems biology approach to medicine. However, these models need to be updated to reflect the latest available knowledge of the underlying pathways. We developed a mathematical model of the insulin signal transduction pathway by expanding the last major previously reported model and incorporating pathway components elucidated since the original model was reported. Furthermore, we show that inputting gene expression data of key components of the insulin signal transduction pathway leads to sensible predictions of glucose clearance rates in agreement with reported clinical measurements. In one set of simulations, our model predicted that glycerol kinase knockout mice have reduced GLUT4 translocation, and consequently, reduced glucose uptake. Additionally, a comparison of our extended model with the original model showed that the added pathway components improve simulations of glucose clearance rates. We anticipate this expanded model to be a useful tool for predicting insulin sensitivity in mammalian tissues with altered expression protein phosphorylation or mRNA levels of insulin signal transduction pathway components.

Lack of impact of angiotensin-converting enzyme gene polymorphism and salt intake on insulin resistance and limb blood flow.

We postulated the mechanism for the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and insulin sensitivity might relate to changes in blood flow regulation. We studied the association of this polymorphism with insulin action, and insulin-mediated changes in limb blood flow (LBF), under conditions of high and low salt intake. We also studied effects of genotype and salt loading on renin-angiotensin-aldosterone system (RAAS) activity. Twenty people with (10 I/I; 10 D/D) and 23 without (10 I/I; 13 D/D), type 2 diabetes were studied during 6 days of 40 mmol/day and 220 mmol/day sodium diet in a randomized, double-blind cross-over fashion. On the sixth day of each condition, we measured 24-h blood pressure, plasma volume, LBF and insulin sensitivity during hyperinsulinaemic clamp at low (40 mU/m(2) /min) and high (600 mU/m(2) /min) dose insulin infusion. Salt intake variation produced greater effects on the renin-angiotensin-aldosterone system than ACE genotype. Diabetes status and insulin infusion were associated with differences in the metabolic clearance rate of glucose, (P < 0·001 for each) and insulin infusion increased LBF (P < 0·001). However, ACE genotype and salt intake had no consistent impacts on either variable in nondiabetic and diabetic subgroups, or in the combined group. Reported differences in insulin sensitivity between ACE genotypes were not found in this study under strict regulation of sodium intake. Insulin sensitivity was also unaffected in either group by sodium loading. ACE genotype and salt status do not impact on insulin sensitivity through changes in limb blood flow during hyperinsulinaemia.

Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: A cross-sectional pilot study

Formerly obese patients having undergone Roux-en-Y gastric bypass (RYGB) display both an accelerated digestion and absorption of carbohydrate and an increased plasma glucose clearance rate after meal ingestion. How RYGB effects postprandial kinetics of dietary lipids has yet not been investigated. Plasma triglyceride (TG), apoB48, total apoB, bile acids (BA), fibroblast growth factor 19 (FGF19), and cholecystokinin (CCK) were measured in post-absorptive conditions and over 4-h following the ingestion of a mixed test meal in a cross-sectional, pilot study involving 11 formerly obese female patients 33.8 ± 16.4 months after RYGB surgery and in 11 weight- and age-matched female control participants. Compared to controls, RYGB patients had faster (254 ± 14 vs. 327 ± 7 min, p < 0.05) and lower (0.14 ± 0.04 vs. 0.35 ± 0.07 mM, p < 0.05) peak TG responses, but their peak apoB48 responses tended to be higher (2692 ± 336 vs. 1841 ± 228 ng/ml, p = 0.09). Their postprandial total BA concentrations were significantly increased and peaked earlier after meal ingestion than in controls. Their FGF19 and CCK concentrations also peaked earlier and to a higher value. The early postprandial apoB48 and BA responses indicate that RYGB accelerated the rate of dietary lipid absorption. The lower postprandial peak TG strongly suggests that the RYGB simultaneously increased the clearance of TG-rich lipoproteins. NCT01891591.

Interaction between milk allowance and fat content of the starter feed on performance of Holstein calves

Sixty-six Holstein male calves [42±6.0kg of body weight (BW) and 12±3.1 d of age] were housed individually and allocated to 1 of 4 treatments following a 2 × 2 factorial complete randomized design to assess the potential interaction between milk replacer (MR) allowance and fat content in the starter feed. Thus, 4 treatments were evaluated: a low-fat (4.1% fat; LF) starter feed offered along with 4L/d of MR (4LF), a high-fat (11.2% fat; HF) starter feed plus 4L/d of MR (4HF), a LF starter feed offered with 6L/d of MR (6LF), and an HF starter feed offered with 6L/d of MR (6HF). Calves were fed either 4 or 6L/d of MR (25% crude protein and 19.2% fat) in 2 offers (0800 and 1630h) and had ad libitum access to either an LF or an HF starter feed (21.4 and 22.3% crude protein). Calves were weaned at wk 6 of study by halving the daily MR allowance for 1 wk. Individual MR and starter feed intakes were recorded daily and BW was determined weekly. A glucose tolerance test was performed on d 30 of study to evaluate the effects of increased energy provision on glucose metabolism. Apparent feed digestibility was measured for the last 5 d of study. Overall, fat content of starter feed had no effect on solid feed intake. However, during wk 8 of study (after weaning), calves in the LF treatment had greater starter feed intake than HF calves. Calves on 6L/d of MR had greater BW than calves fed 4L/d from the second week of study until weaning. After weaning, 6LF calves had lesser BW than 6HF calves. Calves on 6L/d of MR had greater average daily gain than calves fed 4L/d, and 6HF calves tended to have the greatest average daily gain. Glucose clearance rate tended to be lesser for HF than for LF calves. In conclusion, offering 6L/d of MR increased growth performance before weaning and, when offering 6L/d of MR, feeding a high-fat starter feed resulted in the greatest BW after weaning.

The Acute Effects of Interval- Vs Continuous-Walking Exercise on Glycemic Control in Subjects With Type 2 Diabetes: A Crossover, Controlled Study

Glycemic control improves with physical activity, but the optimal exercise mode is unknown. The objective of the study was to determine whether interval-based exercise improves postprandial glucose tolerance and free-living glycemia more than oxygen consumption- and time duration-matched continuous exercise. This was a crossover, controlled study with trials performed in randomized order. The study was conducted in hospitalized and ambulatory care. PATIENTS diagnosed with type 2 diabetes mellitus (n=10, no withdrawals) participated in the study. Subjects performed three 1-hour interventions: 1) interval walking (IW; repeated cycles of 3 min of slow and fast walking); 2) continuous walking (CW); and 3) control (CON). Oxygen consumption (VO2) was measured continuously to match mean VO2 between exercise sessions (∼75% VO2peak). A mixed-meal tolerance test (MMTT; 450 kcal, 55% carbohydrate) with stable glucose isotopic tracers was provided after each intervention, and glucose kinetics were measured during the following 4 hours. Free-living glycemic control was assessed for approximately 32 hours after the MMTT using continuous glucose monitoring. VO2 was well matched between the exercise interventions. IW decreased the mean and maximal incremental plasma glucose during the MMTT when compared with the CON (mean 1.2 ± 0.4 vs 2.0 ± 0.5 mmol/L, P < .001; maximal 3.7 ± 0.6 vs 4.6 ± 0.7 mmol/L, P = .005) and mean when compared with CW (1.7 ± 0.4 mmol/L, P = .02). No differences in the mean or maximal incremental plasma glucose values were seen between the CW and CON. The metabolic clearance rate of glucose during the MMTT was increased in the IW compared with CW (P = .049) and CON (P < .001). Continuous glucose monitoring mean glucose was reduced in IW compared with CW for the rest of the intervention day (8.2 ± 0.4 vs 9.3 ± 0.7 mmol/L, P = .03), whereas no differences were found between IW and CW the following day. One interval-based exercise session improves glycemic control in type 2 diabetes mellitus subjects when compared with an oxygen consumption- and time duration-matched continuous exercise session.

Chickens from lines artificially selected for juvenile low and high body weight differ in glucose homeostasis and pancreas physiology

Artificial selection of White Plymouth Rock chickens for juvenile (day 56) body weight resulted in two divergent genetic lines: hypophagic low weight (LWS) chickens and hyperphagic obese high weight (HWS) chickens, with the latter more than 10-fold heavier than the former at selection age. A study was designed to investigate glucose regulation and pancreas physiology at selection age in LWS chickens and HWS chickens. Oral glucose tolerance and insulin sensitivity tests revealed differences in threshold sensitivity to insulin and glucose clearance rate between the lines. Results from real-time PCR showed greater pancreatic mRNA expression of four glucose regulatory genes (preproinsulin, PPI; preproglucagon, PPG; glucose transporter 2, GLUT2; and pancreatic duodenal homeobox 1, Pdx1) in LWS chickens, than HWS chickens. Histological analysis of the pancreas revealed that HWS chickens have larger pancreatic islets, less pancreatic islet mass, and more pancreatic inflammation than LWS chickens, all of which presumably contribute to impaired glucose metabolism.

An insulin-like growth factor found in hepatopancreas implicates carbohydrate metabolism of the blue crab Callinectes sapidus

Hyperglycemia that is caused by the release of crustacean hyperglycemic hormone (CHH) from the sinus gland to hemolymph is one of the hallmark physiological phenomena, occurring in decapod crustaceans experiencing stressful conditions. However, the mechanism(s) by which such elevated glucose levels return to resting levels is still unknown. Interestingly, noted is a difference in the clearance rate of hemolymph glucose between adult females and adult males of the blue crab, Callinectes sapidus: the former with more rapid clearance than the latter. The presence of an endogenous-insulin-like molecule is suggested in C. sapidus because an injection of bovine insulin, significantly reduces the levels of hemolymph glucose that were previously elevated by emersion stress or the glucose injection. Using 5′ and 3′ RACE, the full-length cDNA of an insulin-like molecule is isolated from the hepatopancreas of an adult female C. sapidus and shows the same putative sequence of an insulin-like androgenic gland factor (IAG) but differs in 5′ and 3′ UTR sequences. A knock-down study using five injections of double-stranded RNA of CasIAG-hep (dsRNA-CasIAG-hep, 10μg/injection) over a 10-day period reduces CasIAG-hep expression by ∼50%. The levels of hemolymph glucose are also kept higher in dsRNA-CasIAG-hep injected group than those treated with dsRNA-green fluorescent protein (dsRNA-IAG-hep) or saline. Most importantly, the hepatopancreas of dsRNA-CasIAG-hep injected animals contains amounts of carbohydrate (glucose, trehalose, and glycogen) significantly lower than those of control groups, indicating that the function of CasIAG-hep in carbohydrate metabolism in crustaceans is similar to carbohydrate metabolism in vertebrates.

Effect of preeclampsia on insulin sensitivity

Objective:The objective of this study is to investigate whether preeclampsia is associated with exacerbation of insulin resistance.Materials and Methods:The study was conducted over a period of 7 months from November 2011 to May 2012, in a tertiary care hospital attached to a medical college. A total of 14 pregnant women in the third trimester with preeclampsia were recruited for this study and 14 well-matched normotensive women in the third trimester were taken as control. 15 g, 50% dextrose load was given intravenously and blood sampling was carried out for glucose and insulin levels up to 3 h afterward. Minimal model analysis of glucose and insulin levels was performed to arrive at results.Results:No significant changes in mean age, body mass index, gestation, serum lipid and progesterone, cortisol and androgen concentrations were recognized. No significant difference was found between the glucose decay curves and between the glucose clearance rate K, in the two groups (preeclamptic vs. normotensive: 2.1 ± 0.2 vs. 2.2 ± 0.3; P = 0.48). Therefore, there was a small but prolonged decrease in the insulin response of women with preeclampsia compared with women in the normotensive group.Conclusion:Preeclampsia per se is not a risk factor for development of insulin resistance.

The Diabetic Brain During Hypoglycemia

Many factors impact the fluctuating rates of glucose flux and clearance in one’s daily life (meal size and composition, gastric emptying rate, physical activity, etc.). With this constantly changing need for circulating insulin abundance, it is challenging for the treatment strategy to be entirely successful in individuals with type 1 diabetes (T1D), and transient periods of hypoglycemia occur. Humans have evolved metabolic strategies to cope with hypoglycemia, and these include counter-regulatory endocrine responses to increase hepatic glucose production as well as selection of alternative fuels for mitochondrial respiration. The central nervous system can use glycolytic end products that were produced by other tissues (circulating lactate) as well as ketones to some extent. The ability to take up and oxidize these alternative fuels is likely critical for tolerance of and survival through hypoglycemia. The traditional view was that glycolysis makes pyruvate and that only under anaerobic conditions would lactate be generated. It is now recognized that glycolysis makes lactate even under fully aerobic conditions because of the intrinsic kinetic properties of lactate dehydrogenase, which rapidly interconverts pyruvate and lactate and favors lactate on a mass basis. Thus, lactate can be considered the major product of glycolysis even when the fate of glycolytic carbon is primarily mitochondrial oxidation. The basal lactate concentration in tissues and arterial circulation is at least 10 times greater than pyruvate and even higher under stresses that increase the glycolytic rate (1,2), so lactate is the primary shuttling form of glycolytic end products through the cytoplasm and through the circulation from one organ to another. The liver releases glucose to share its carbohydrate fuel depot with other tissues. …