Maintenance Of Blood Glucose Concentrations Research Articles

Myths and methodologies: Assessing glycaemic control and associated regulatory mechanisms in human physiology research.

Accurate measurements of glycaemic control and the underpinning regulatory mechanisms are vital in human physiology research. Glycaemic control is the maintenance of blood glucose concentrations within optimal levels and is governed by physiological variables including insulin sensitivity, glucose tolerance and β-cell function. These can be measured with a plethora of methods, all with their own benefits and limitations. Deciding on the best method to use is challenging and depends on the specific research question(s). This review therefore discusses the theory and procedure, validity and reliability and any special considerations of a range common methods used to measure glycaemic control, insulin sensitivity, glucose tolerance and β-cell function. Methods reviewed include glycosylated haemoglobin, continuous glucose monitors, the oral glucose tolerance test, mixed meal tolerance test, hyperinsulinaemic euglycaemic clamp, hyperglycaemic clamp, intravenous glucose tolerance testand indices derived from both fasting concentrations and the oral glucose tolerance test. This review aims to help direct understanding, assessment and decisions regarding which method to use based on specific physiology-related research questions.

A feedback control of insulin signaling by transcription factor HMG box‐containing protein 1 (HBP1) in adipocytes

Adipocytes are sensitive to insulin control of cellular glucose utilization, thereby facilitating the maintenance of blood glucose concentration. Previously we demonstrated that transcription factor HBP1 is highly expressed in differentiated adipocytes, which, together with CCAAT/enhancer‐binding proteins C/EBPβ and C/EBPα, regulates adipocyte differentiation. To further gain insight into the biological role of HBP1 in mature adipocytes, here, we employed mouse embryonic fibroblast (MEF)‐derived adipocytes to test the hypothesis that HBP1 might regulate insulin sensitivity in adipocytes. First, suppression of HBP1 by siRNA‐mediated gene silencing significantly attenuated glucose uptake as shown by 2‐NBDG glucose uptake assay. We then examined the insulin‐signaling pathway to unravel the molecular mechanism by which HBP1 commands adipocytes to take up glucose. Under serum starvation, the transcription of insulin receptor (InR) was increased, whereas HBP1 silencing down‐regulated the expression of InR in adipocytes, indicating that HBP1 is able to promote insulin sensitivity under insulin insufficient state. However, the addition of insulin (2 nM for 6 h) led to a significant decrease in the transcription of HBP1, InR, and IRS1/2 (insulin receptor substrate 1/2). Moreover, HBP1 siRNA led to increased level of p‐S307 IRS‐1 that is associated with blockade of the insulin signaling, and also resulted in an unexpected induction of glucose transporter 4 (GLUT4). The upregulation of GLUT4 may function as a compensation mechanism for the defective insulin signaling caused by HBP1 silencing. Taken as a whole, our results reveal a key feedback control mechanism for HBP1 in regulating insulin signaling and glucose metabolism.Support or Funding InformationThis work was supported by the grant to MOST 105‐2320‐B‐039‐044‐MY2 C‐Y Huang.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Decreased intracellular granule movement and glucagon secretion in pancreatic α cells attached to superior cervical ganglion neurites

Autonomic neurons innervate pancreatic islets of Langerhans and participate in the maintenance of blood glucose concentrations by controlling hormone levels through attachment with islet cells. We previously found that stimulated superior cervical ganglia (SCG) could induce Ca2+ oscillation in α cells via neuropeptide substance P using an in vitro co-culture model. In this study, we studied the effect of SCG neurite adhesion on intracellular secretory granule movement and glucagon secretion in α cells stimulated by low glucose concentration. Spinning disk microscopic analysis revealed that the mean velocity of intracellular granules was significantly lower in α cells attached to SCG neurites than that in those without neurites under low (2mM), middle (10mM), and high (20mM) glucose concentrations. Stimulation by a low (2mM) glucose concentration significantly increased glucagon secretion in α cells lacking neurites but not in those bound to neurites. These results suggest that adhesion to SCG neurites decreases low glucose-induced glucagon secretion in pancreatic α cells by attenuating intracellular granule movement activity.

Muscle microvascular blood flow responses in insulin resistance and ageing.

Insulin resistance plays a key role in the development of type2 diabetes. Skeletal muscle is the major storage site for glucose following a meal and as such has a key role in maintenance of blood glucose concentrations. Insulin resistance is characterised by impaired insulin-mediated glucose disposal in skeletal muscle. Multiple mechanisms can contribute to development of muscle insulin resistance and our research has demonstrated an important role for loss of microvascular function within skeletal muscle. We have shown that insulin can enhance blood flow to the microvasculature in muscle thus improving the access of glucose and insulin to the myocytes to augment glucose disposal. Obesity, insulin resistance and ageing are all associated with impaired microvascular responses to insulin in skeletal muscle. Impairments in insulin-mediated microvascular perfusion in muscle can directly cause insulin resistance, and this event can occur early in the aetiology of this condition. Understanding the mechanisms involved in the loss of microvascular function in muscle has the potential to identify novel treatment strategies to prevent or delay progression of insulin resistance and type2 diabetes.

Amylin and Selective Glucoregulatory Peptide Alterations during Prolonged Exercise

Amylin is a pancreatic β-cell peptide that facilitates the regulation of blood glucose concentration by inhibiting release of glucagon and modulating gastric emptying. Prolonged exercise may alter amylin and aid in the maintenance of blood glucose concentration; however, no studies have investigated the effects of prolonged exercise on amylin. This study aimed to determine the effects of 90 min of treadmill exercise on amylin and other glucoregulatory hormone responses in a postprandial state. Eight young healthy males completed a preliminary trial for VO2max and body composition determination and subsequent experimental and control trials in a counterbalanced manner. The experimental trial subjects arrived at the laboratory at 8:00 a.m., 1 h after consumption of a standard nutrient beverage (Ensure Plus®). At 9:50 a.m., subjects initiated 90 min of treadmill exercise at 60% of VO2max. Blood samples were collected twice before exercise, every 18 min during exercise, and every 20 min during 1 h of recovery. A resting control trial was conducted in an identical manner without VO2 assessment. Plasma glucose and leptin concentrations remained stable across exercise, whereas lactate significantly increased to peak at 18 min of exercise then gradually declined. Amylin, insulin, and C-peptide values significantly declined over the trials, with no difference between exercise and control days. Glucagon area-under-the-curve concentrations were significantly greater during the exercise than the control trials. There was a significant time effect and trial effect for cortisol with a higher concentration during the experimental trial than during the control trial. In a postprandial state, prolonged exercise stimulates glucagon and cortisol increases that are associated with stable blood glucose and leptin concentrations; however, similar to postprandial state control condition, insulin, C-peptide, and amylin concentrations decline.

Glycemic Control in the Intensive Care Unit and during the Postoperative Period

Glycemic Control in the Intensive Care Unit and during the Postoperative Period

Physiological and Metabolic Aspects of Very Prolonged Exercise with Particular Reference to Hill Walking

Hill walking is a popular recreational activity in the developed world, yet it has the potential to impose severe stress simultaneously upon several regulatory systems. Information regarding the physiological strain imposed by prolonged walking outdoors in adverse climatic conditions was reported almost four decades ago and recent research has extended some of this work. These data indicate that once the walker fatigues and starts to slow or stops walking altogether, the rate of heat production falls dramatically. This decrease alone predisposes to the development of hypothermia. These processes, in adverse weather conditions and/or during periods when the level of exertion is low (with low heat production), will be accelerated. Since the majority of walkers pursue this activity in groups, the less fit walkers may be more susceptible to fatigue when exercising at a higher relative intensity compared with their fitter counterparts. The best physiological offset for hypothermia is to maintain heat production by means of exercise, and so fatigue becomes a critical predisposing factor; it is as important to facilitate heat loss, especially during periods of high exertion, as it is to maintain heat production and preserve insulation. This can be partly achieved by clothing adjustments and consideration of the intensity of exercise. Failure to provide adequate energy intake during hill walking activities has been associated with decreased performance (particularly with respect to balance) and impaired thermoregulation. Such impairments may increase susceptibly to both fatigue and injury whilst pursuing this form of activity outdoors. The prolonged low to moderate intensity of activity experienced during a typical hill walk elicits marked changes in the metabolic and hormonal milieu. Available data suggest that during hill walking, even during periods of acute negative energy balance, blood glucose concentrations are maintained. The maintenance of blood glucose concentrations seems to reflect the presence of an alternative fuel source, a hormonally induced increase in fat mobilisation. Such enhancement of fat mobilisation should make it easier to maintain blood glucose by decreasing carbohydrate oxidation and promoting gluconeogenesis, thus sparing glucose utilisation by active muscle. During strenuous hill walking, older age walkers may be particularly prone to dehydration and decreased physical and mental performance, when compared with their younger counterparts. In summary, high rates of energy expenditure and hypohydration are likely to be closely linked to the activity. Periods of adverse weather, low energy intake, lowered fitness or increased age, can all increase the participants' susceptibility to injury, fatigue and hypothermia in the mountainous environment.

Modifying cardiovascular risk in diabetes mellitus.

DIABETES mellitus affects an estimated 35 million people in the United States, and the disease prevalence is predicted to increase by nearly 200% in the next several decades. As a result, anesthesiologists will be confronted with an increasing population of patients undergoing anesthesia and surgery who are at risk for ischemic heart disease. Hyperglycemia Predicts Cardiovascular Risk Diabetes is a significant predictor of perioperative cardiovascular morbidity and mortality, but few studies have evaluated methods to modify this risk. Compelling evidence indicates that aggressive management of diabetes may substantially decrease the adverse consequences of myocardial ischemia and infarction. The direct impact of hyperglycemia on cardiovascular mortality in patients with and without diabetes is a central theme of current research, and several investigations conducted during the past 20 yr demonstrated that mortality resulting from acute myocardial infarction (AMI) is increased if blood glucose concentration is elevated at the time of hospital admission. 1 These findings were confirmed in a recent prospective analysis of 336 consecutive patients admitted with AMI. 2 One-year mortality was 9% for patients with AMI and normal admission blood glucose values. In contrast, patients with hyperglycemia (blood glucose concentrations of 121 15, 168 13, and 282 65 mg/dl) on admission demonstrated substantial increases (P 0.005) in mortality to 13, 30, and 44%, respectively. 2 The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial addressed the prognostic significance of hyperglycemia in patients with type 1 and 2 diabetes and AMI. 3 A nearly linear relationship between blood glucose concentration on admission and long-term mortality was observed in conventionally treated patients in this randomized clinical trial (mortality rates of 35, 40, and 55% at blood glucose concentrations of 235, 235–298, and 298 mg/dl, respectively). A direct relationship between fasting blood glucose concentration and the risk of sustaining a cardiovascular event (e.g., sudden cardiac death, AMI, or cerebrovascular accident) has been demonstrated in a meta-regression analysis of data from 20 studies involving more than 95,000 patients. 4 The risk associated with fasting blood glucose concentrations was linear and extended below the threshold used to define diabetes. A fasting blood glucose value of only 110 mg/dl was associated with an increased relative risk of a cardiovascular event. Similarly, the odds ratio of AMI was increased to 1.5, 3.4, and 6.0 at fasting blood glucose concentrations of approximately 90, 110, and greater than 115 mg/dl, respectively. 5 Another large cohort study indicated that glycosylated hemoglobin (HbA1c) concentration, but not the presence of diabetes, predicted an increase in mortality. 6 The risk of all-cause mortality increased by a factor of 1.46 for every 1% increase in HbA 1c when male patients with diabetes, those with HbA 1c concentrations greater than 7%, or patients with a history of heart disease or stroke were excluded from the multivariate regression model. Similarly, creatinine kinase concentrations were higher in patients with hyperglycemia admitted with AMI compared with those with normal blood glucose levels. 2 These data demonstrate a striking relationship

The kinetic properties of liver glucokinase and its function in glucose physiology as a model for the comprehensive study of enzymes' kinetic parameters and reversible inhibitors

AbstractGlucokinase is a key enzyme in carbohydrate metabolism in mammals. Particularly relevant is the involvement of the liver enzyme for the maintenance of blood glucose concentrations. In playing this key role, the occurrence of normal kinetic parameters of liver glucokinase is critical. Modification of Km and/or Vmax results in pathological situations occurring with hypo‐ or hyperglycemia. Based on this, an exercise is proposed in which different mice cell lines with abnormalities in glucose utilization are analyzed to determine the metabolic alteration at a molecular level. The student must determine the cause of abnormality by processing the kinetic data. Also, the characterization of different compounds that are reversible inhibitors of the enzyme from kinetic data is required to identify a drug that can correct the pathology in each case. One major objective of the problem is to learn about the meaning of kinetic parameters of enzymes, as well as the action of different types of reversible inhibitors. © 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved.

The kinetic properties of liver glucokinase and its function in glucose physiology as a model for the comprehensive study of enzymes’ kinetic parameters and reversible inhibitors

Glucokinase is a key enzyme in carbohydrate metabolism in mammals. Particularly relevant is the involvement of the liver enzyme for the maintenance of blood glucose concentrations. In playing this key role, the occurrence of normal kinetic parameters of liver glucokinase is critical. Modification of Km and/or Vmax results in pathological situations occurring with hypo- or hyperglycemia. Based on this, an exercise is proposed in which different mice cell lines with abnormalities in glucose utilization are analyzed to determine the metabolic alteration at a molecular level. The student must determine the cause of abnormality by processing the kinetic data. Also, the characterization of different compounds that are reversible inhibitors of the enzyme from kinetic data is required to identify a drug that can correct the pathology in each case. One major objective of the problem is to learn about the meaning of kinetic parameters of enzymes, as well as the action of different types of reversible inhibitors.

The effects of starvation on plasma free amino acid and glucose concentrations in lake sturgeon

The effect of starvation on the metabolism of the lake sturgeon Acipenser fulvescens was examined by measuring haematocrit, plasma glucose concentrations, and plasma free amino acids. Plasma was sampled on day 0, 10, 20, 45 and 60 of a 60‐day starvation period. Haematocrit was observed to decrease with starvation indicating a decreased oxygen carrying capacity of the blood. Plasma glucose levels differed only at day 10, with a decrease in blood glucose level in the starved group. No differences were detected between groups for alanine, aspartate, and serine, while elevated levels were observed for glutamine throughout the experiment. An increase in arginine, tyrosine, valine, methionine, tryptophan, phenylalanine, glutamate, glycine, isoleucine, histidine and leucine, concentrations were observed after 45 days of starvation. The maintenance, or increased plasma levels, of glucogenic amino acids in combination with the maintenance of blood glucose concentrations indicates active gluconeogenic processes in the liver supported by muscle proteolysis.

Type I Glycogen Storage Disease: A Metabolic Basis for Advances In Treatment

Studies suggest that the clinical and biochemical abnormalities present in GSD-I result from an excess rate of glycogenolysis secondary to a decrease in blood glucose concentrations below 70 mg/dl. The lack of glucose-6-phosphatase activity prevents hepatic release of glycogen to glucose and continued stimulation of glycogenolysis causes excessive formation of glucose-6-phosphate and secondarily increases lactate, triglyceride and uric acid. In addition, abnormal platelet function, prolonged bleeding time and impaired growth are prominent features of the illness. Biochemical and clinical aberrations in GSD-I can be substantially improved by treatment aimed at decreasing the hepatic stimulus for glycogenolysis by maintenance of blood glucose concentration between 70 and 150 mg/dl. This is most effectively done by total parenteral nutrition or continuous intragastric infusion of a high-glucose diet (i. e., Vivonex High Nitrogen or Precision LR). The equally effective, more practical and most acceptable method of maintaining blood glucose levels is continuous infusion of the diet at night for 8-12 hours, followed by high-starch feedings every 3 hours while awake. This treatment has been very effective in providing the necessary milieu for normal growth and development in 7 patients for 4 years.

Plasma amino acid levels and development of hepatic gluconeogenesis in the newborn rat.

The metabolism of endogenous and exogenous amino acids has been characterized during a 16-h fast after birth in the rat. Eighteen of 22 amino acids showed a decrease in plasma concentration up to 16 h, the most profound and sustained changes affecting those quantitatively important in gluconeogenesis. The hepatic accumulation of injected [14C]aminoisobutyric acid showed a progressive rise after birth. The in vivo conversion of 14C-labeled lactate, alanine, serine, and glutamine to [14C]glucose increased for 6 h, but all except glutamine showed a decline by 16 h. The in vitro conversion of several gluconeogenic substrates (10mM), however, increased with time in each instance. These data confirm that the capacity for hepatic gluconeogenesis and maintenance of blood glucose concentration appears immediately after birth. Nevertheless, profound hypoglycemia recurs at 16 h and responds only minimally and transiently to exogenous gluconeogenic substrate loads. In contrast, the fed newborn maintains normoglycemia, higher endogenous amino acid levels, and the capacity for substrate conversion at this time. The mechanism for stimulation of hepatic gluconeogenic pathways thus is present in both fasted and fed neonatal rats. However, owing to insufficient energy sources to sustain gluconeogenesis and to inadequate gluconeogenic substrate, the rat is unable to maintain normoglycemia if fasted 16 h.