Regulation Of Glucose Levels Research Articles

Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse model of Alzheimer's disease

We previously reported aberrant stress responses and impaired glucose tolerance in transgenic Tg2576 mice, a model of Alzheimer's disease (AD). Here we report that by 8 months of age, Tg2576 mice had lower basal serum insulin concentrations and exhibited a delayed insulin-induced reduction in blood glucose levels relative to wild-type mice. However, the basal levels of blood glucose and percent glycosylated hemoglobin (%HbA1c) were similar between the two groups of mice. While the basal levels of serum corticosterone were similar between Tg2576 and wild-type mice, an overnight fasting caused a greater rise in serum corticosterone levels and an excessive reduction in serum insulin concentrations in the transgenics. At 9 months of age, we began administering Tg2576 mice rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma that increases peripheral insulin sensitivity, and after 6 weeks of administration the Tg2576 mice had the same response to insulin and increase in serum corticosterone levels after an overnight fast as did wild-type mice. By 13 months of age, untreated Tg2576 mice had become hyperinsulinemic, in contrast to Tg2576 mice administered rosiglitazone for 4 months where the serum insulin concentrations were maintained at levels observed in wild-type mice. These results provide evidence for a relationship between insulin resistance, impaired regulation of insulin and glucose levels, and aberrant stress responses in Tg2576 mice.

Pathophysiology, Homeostasis and Nursing

Despite being predominantly aimed at g pre-registration students, this book is still highlf relevant to nurses undertaking post-registration study. The content focuses on physiology and how the body maintains homeostasis, and advises on the nursing care of patients with altered homeostasis. Seven key body mechanisms controlled by homeostasis are highlighted. The book is presented in a logical, coherent format that enables the reader to easily digest the subject matter. However, I was disappointed that it only superficially covered the regulation of glucose levels and heart rate - perhaps these mechanisms warrant their own chapters. The fluid balance chapter could have more emphasis on the role of the kidney also. Overall though, this is an excellent resource and should be an essential read for a; nursing students.

Factors influencing insulin secretion from encapsulated islets.

Adequate regulation of glucose levels by a microencapsulated pancreatic islet graft requires a minute-to-minute regulation of blood glucose. To design such a transplant, it is mandatory to have sufficient insight in factors influencing the kinetics of insulin secretion by encapsulated islets. The present study investigates factors influencing the glucose-induced insulin response of encapsulated islets in vitro. We applied static incubations and did the following observations. (i) Small islets (90-120 microm) showed a similar instead of a lower glucose-induced insulin response, suggesting that inclusion of only small islets, which are associated with lower protrusion and failing rates, has no consequences for the functional performance of the graft. (ii) A capsule diameter of 800 microm showed identical rather than lower glucose-induced insulin responses as smaller, 500-microm capsules. (iii) Capsule membranes constructed with a conventional permeability interfered with diffusion of insulin, as illustrated by a lower response of islets in capsules with a 10-min poly-L-lysine (PLL) membrane than islets in capsules with a 5-min PLL membrane. (iv) Irrespective of the tested porosity, the capsules provided sufficient immunoprotection because the 10-min PLL membranes did block diffusion of the cytokines IL-1beta (17 kDa) and TNF-alpha (70 kDa) while the 5-min PLL membranes interfered with the diffusion of the vast majority of the cytokines. We conclude that capsules containing small islets (90-120 microm) and a membrane with a lower permeability than routinely applied is preferred in order to obtain a graft with adequate glucose-induced insulin responses.

Xenogeneic transplantation of porcine islets: an overview

The extreme demand for human organs or tissues for transplantation has driven the search for viable alternatives. Pigs are considered a possible source of tissue for a number of reasons including shared physiology, plentiful supply, short gestation, and, more recently, the generation of transgenic animals. Porcine islets show promise as a source of islets for the treatment of type 1 diabetes mellitus. Porcine islets regulate glucose levels in the same physiologic range as humans, and porcine insulin has been used for years as an exogenous source of insulin for glucose control. In this review, we discuss the advantages and disadvantages of the use of adult or neonatal porcine islets, the immunologic challenges facing transplantation of xenogeneic islets, and the concerns regarding transmission of infectious agents between species. Porcine islets isolated from both adult and neonatal pigs are capable of restoring euglycemia in experimental animal models of diabetes. Adult islets are more difficult to isolate, whereas neonatal islets have great proliferation potential but require several weeks to function posttransplantation. Xenogeneic islets are susceptible to complement-mediated lysis after the binding of preformed natural antibodies and cellular immunity involving both macrophages and CD4+ T cells. In addition, the potential for transmission of porcine endogenous retroviruses, porcine cytomegalovirus, and porcine lymphotropic herpesvirus type 1 are all concerns that must be addressed. Despite the challenges facing xenotransplantation, the extreme need for donor organs and tissues continues to drive progress toward overcoming the unique issues associated with transplantation between species.

Wiring the Brain with Insulin

The activities of insulin in regulating glucose levels and controlling many other physiological processes are well documented. Surprisingly, as [Dickson][1] comments in his Perspective, insulin has now been found to participate in guiding photoreceptor cell axons from the retina to the brain during development of the visual system in the fruit fly ([ Song et al .][2]). [1]: http://www.sciencemag.org/cgi/content/full/300/5618/440 [2]: http://www.sciencemag.org/cgi/content/short/300/5618/502

CNS sensing and regulation of peripheral glucose levels

It is clear that the brain has evolved a mechanism for sensing levels of ambient glucose. Teleologically, this is likely to be a function of its requirement for glucose as a primary metabolic substrate. There is no question that the brain can sense and mount a counterregulatory response to restore very low levels of plasma and brain glucose. But it is less clear that the changes in glucose associated with normal diurnal rhythms and feeding cycles are sufficient to influence either ingestive behavior or the physiologic responses involved in regulating plasma glucose levels. Glucosensing neurons are clearly a distinct class of metabolic sensors with the capacity to respond to a variety of intero- and exteroceptive stimuli. This makes it likely that these glucosensing neurons do participate in physiologically relevant homeostatic mechanisms involving energy balance and the regulation of peripheral glucose levels. It is our challenge to identify the mechanisms by which these neurons sense and respond to these metabolic cues.

Nutritional Management of Neonatal and Infant Liver Disease

After completing this article, readers should be able to: 1. Describe the caloric requirements of a neonate who has chronic liver disease. 2. Identify the vitamin and mineral deficiencies associated with cholestasis and the methods used to correct these deficits. 3. Describe the relationship between total parenteral nutrition and the development of chronic liver disease. 4. Delineate the relationship between malnutrition at the time of liver transplantation and subsequent morbidity and mortality. 5. List the best measurements of nutrition assessment in infants who have chronic liver disease. The liver is involved in many of the body’s metabolic processes, including: regulation of protein, fat, and carbohydrate metabolism; vitamin storage and activation; and detoxification and excretion of waste products. The healthy liver synthesizes and excretes bile salts. With cholestatic liver diseases, poor bile flow results in fat malabsorption because micelles, which solubilize long-chain fatty acids, cannot form without bile salts. Fat malabsorption results in enteric losses of the fat-soluble vitamins A, D, E, and K. Impaired liver function can lead to nutrient deficiencies and eventually protein-energy malnutrition. All of these factors, combined with the common symptoms of anorexia and poor dietary intake, make malnutrition common in chronic liver disease, particularly if it occurs in infants, who are more vulnerable to the debilitating effects of malnutrition because of their higher energy and growth requirements. A wide range of deficits occurs in most chronic liver diseases of children (Table 1⇓ ). Malnutrition itself may induce further derangements of liver function because the liver requires energy for a number of synthetic, storage, and detoxification functions. View this table: Table 1. Nutritional Risk Factors in Acute and Chronic Liver Disease The need for aggressive, early nutrition support in neonates has been well established and discussed extensively. Some centers routinely use a “standardized” approach to nutrition support; we use a “tailored” approach that entails parenteral or …

On the mode of action of methionine enkephalin, FK 33-824 and naloxone in regulating the hemolymph glucose level in the fresh water field crab Oziotelphusa senex senex.

The possible involvement of opioid system in the regulation of hemolymph glucose level in the fresh water crab Oziotelphusa senex senex Fabricius, was investigated. Opioid agonist and antagonist was also used in addition to methionine-enkephalin itself. Injection of the opioid, methionine-enkephalin and FK 33-824 significantly elevated hemolymph glucose level. In contrast, injection of naloxone in to crab resulted in decrease in hemolymph glucose level. Injection of naloxone prior to injection of methionine-enkephalin blocked the hyperglycemic action of methionine-enkephalin. Injection of methionine-enkephalin, FK 33824 and naloxone produced no significant effect on hemolymph glucose level in eyestalk-less crab. The alterations in the intact crab hemolymph glucose level hypothesised to be due to stimulation of release of hyperglycemic hormone during methionine-enkephalin and FK 33824 treatment and blocking of release of hyperglycemic hormone during naloxone treatment from the eyestalks of crab Oziotelphusa senex senex.

Effects of arsenic (V)-chromium (III) interaction on plasma glucose and cholesterol levels in growing rats.

Recent studies have demonstrated interaction between arsenic (As) and chromium (Cr) affecting absorption and/or protein catabolism. In the present study the possible effects of As(V)/Cr(III) interaction on growth rate, organ weight, and the two main organic functions of Cr, i.e., regulation of plasma glucose levels and total plasma cholesterol levels, was examined in weaned male Wistar rats. The diet of 20 rats was supplemented with 5 micrograms of As(V) and/or Cr(III) per gram of food for 10 weeks. As/Cr interaction did not significantly affect growth rates on organ weight:body weight ratios but did decrease total plasma cholesterol levels, though the decrease was not as pronounced as in the group supplemented with Cr alone (p < 0.1). Since supplementation with As(V) produced the opposite effect (96.83 vs. 47.27) (p < 0.01), the combined use of As and Cr may prove beneficial in cases of chronic As(V) intoxication. Supplementation treatment with As(V) and Cr(III) combined had no significant effect on glucose levels, because though As(V) affects Cr tissue levels and thus alters the effect of Cr on plasma cholesterol levels, individual effects of As(V) and Cr(III) are similar, and hence basal glucose levels are unaffected.

Section Review Oncologic, Endocrine &amp; Metabolic: The amylin, CGRP and calcitonin family of peptides

The calcitonins are a group of 32 amino acid, disulphide bridged, C-terminally amidated peptides, first isolated from the thyroid and characterised as hormones which regulate blood calcium levels. Observations on alternative splicing of mRNA derived from the calcitonin gene resulted in the identification of the potent vasodilator: calcitonin gene-related peptide (CGRP), a 37 amino acid, disulphide bridged peptide, again with a C-terminal amide. More recently a third type of peptide, amylin, has been isolated from pancreases of Type 2 diabetics. This also is a 37 amino acid residue, disulphide bridged C-terminally amidated peptide, and acts as a regulator of blood glucose levels in conjunction with insulin. Two other moiecules may also be somewhat related to these: adrenomedullin, which has weak structural homology with CGRP and amylin and shows vasodilatory properties, and maxadilan, which is structurally unrelated but resembles CGRP biologically. This review summarises recent progress on the characterisa...

Regulation of Ca2+ transport by insulin and taurine. Interaction at the level of the Na(+)-Ca2+ exchanger.

In 1983 Lampson et al. 16 and Tokunaga et al. 31 introduced the concept that an interaction must exist between the actions of taurine and those of insulin. The initial studies examining this question focused on the metabolic actions of insulin. Tokunaga et al. 31 found that taurine suppressed insulin secretion in nondiabetic pancreatic islets, suggesting that taurine might serve as a physiological regulator of insulin secretion and plasma glucose levels. They also found that taurine levels increased significantly in diabetic islets, implying that taurine might contribute to the state of hypoinsulinemia and hyperglycemia. Lampson et al. 16 also concluded that taurine influenced plasma glucose levels, but their studies linked the hypoglycemic actions of taurine to a potentiation of insulin-mediated glucose uptake. Lampson et al. 16 also reported that taurine promoted several other insulin sensitive reactions, implying that taurine either facilitated the interaction of insulin with its receptor or increased the production of a putative second messenger of insulin. Subsequent studies revealed that taurine could interact directly with the insulin receptor15, 20. This interaction appeared to be quite specific since insulin was capable of displacing taurine from its binding sites20. Based on these data, Maturo and Kulakowski20 suggested that taurine might exhibit insulin-mimetic activity. However, this notion is inconsistent with a recent observation by Schaffer et al. 30 that insulin, but not taurine, could stimulate Na+-Ca2+ exchanger activity. Yet, the studies by Schaffer et al. 30 did not address the possibility that taurine might function as a general modulator of insulin action.

Alpha 2-adrenoceptors and the regulation of glucose, insulin and amylin levels in diabetic rats

The effects of the selective alpha 2-adrenoceptor agonist UK 14.304 on glucose, insulin and amylin levels were examined in neonatal streptozotocin-induced diabetic rats. UK 14.304 (0.03 to 0.3 mg/kg i.p.) induced a dose-dependent reduction of both insulin and amylin levels in normal rats while UK 14.304 at 0.03 mg/kg had already a maximal effect in diabetic rats. Amylin/insulin molar ratios rose after UK 14.304 administration in diabetic rats but remainded constant in normal rats. The alpha 2-adrenoceptor antagonist deriglidole (3 mg/kg i.p.) slightly increased insulin and amylin levels in the two groups of rats but glucose levels were more markedly decreased in diabetic rats. Deriglidole completely antagonized UK 14.304 (0.1 mg/kg i.p.)-induced changes thereby normalizing amylin/insulin molar ratios in diabetic rats. These results suggest that insulin and amylin are both under inhibitory control via alpha 2-adrenoceptor though the responses may be differentially regulated. It is further suggested that diabetes in the neonatal streptozotocin-induced rat model is associated with a hypersensitivity of the pancreas to alpha 2-adrenoceptor stimulation.

HOST DEFENSES AND SUSCEPTIBILITY TO INFECTION IN PATIENTS WITH DIABETES MELLITUS

The recently completed Diabetes Control and Complications Trial (DCCT) provided compelling evidence that intensive treatment of people with insulin-dependent diabetes mellitus can delay or prevent diabetic microvascular complications. Although not studied in the DCCT, patients with noninsulin-dependent diabetes mellitus likely will benefit from near-normoglycemia. Although it is difficult to prove a similar causal relation between hyperglycemia and infection (this outcome was not looked for in the DCCT), there is substantial in vitro data and evolving clinical studies that support this hypothesis. This information is presented in this article following a review of the regulation of glucose levels.

Alexithymic Characteristics and Metabolic Control in Diabetic and Healthy Adults

Diabetes has long been identified as a disease with possible psychological components. Alexithymia--an inability to express emotions verbally, operational thinking, and a lack of fantasy life--is found in a high proportion of psychosomatic patients. We therefore tested the hypothesis that diabetics would be more alexithymic than controls. In addition, the lack of awareness of affect was hypothesized to have negative consequences for the management of diabetes, as reflected in metabolic glucose control (HbA1). The number of emotion words produced in six imaginative (Thematic Apperception Test) stories was used as the measure of alexithymia, with few words reflecting alexithymic characteristics. Diabetics were found to be significantly more alexithymic than controls. Further, fewer emotion words (alexithymia) was associated with poorer metabolic control. These data suggest that alexithymic characteristics may interfere with a diabetic's ability to manage their illness, and support previous research showing that the suppression of emotions can lead to a difficulty in regulating glucose levels.

The role of α‐ and β‐adrenoceptor subtypes in mediating the effects of catecholamines on fasting glucose and insulin concentrations in the rat

1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma glucose and immunoreactive insulin (IRI) levels has been investigated in normal conscious fasted rats by employing selective agonists and antagonists. 2. Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective alpha 2-adrenoceptor antagonist idazoxan (1.0 mg kg-1), unaltered by non-selective beta-adrenoceptor blockade (propranolol, 1.0 mg kg-1) and potentiated by the selective alpha 1-adrenoceptor antagonist prazosin (0.3 mg kg-1). Adrenaline increased plasma IRI levels in the presence of idazoxan but not in the presence of either prazosin or propranolol. 3. The selective alpha 2-adrenoceptor agonists UK 14304 (0.1 and 0.3 mg kg-1) and BHT-920 (0.2 and 0.5 mg kg-1) elicited dose-dependent hyperglycaemic responses, but did not alter plasma IRI levels. UK 14304 (0.1 mg kg-1)-evoked hyperglycaemia was blocked by idazoxan but not by prazosin. 4. The selective alpha 1-adrenoceptor agonists methoxamine (0.3 mg kg-1) and phenylephrine (0.3 mg kg-1) failed to modify either plasma glucose or IRI levels. 5. Isoprenaline (0.2 mg kg-1) elicited hyperglycaemic and insulinotropic responses which were attenuated by propranolol (1.0 mg kg-1) and the selective beta 2-adrenoceptor antagonist ICI 118551 (1.0 mg kg-1), but not by the beta 1-selective antagonists atenolol (1.0 mg kg-1) and betaxolol (1.0 mg kg-1). 6. None of the antagonists per se affected basal plasma glucose or IRI concentrations, except prazosin (1.0 mg kg-1). 7. The results indicate that adrenoceptors do not appear to be involved in regulating basal plasma glucose and IRI concentrations in the fasted rat. However, the effects of catecholamines on these parameters are mediated by alpha 2- and beta 2-adrenoceptors, whereas alpha,- or beta l-adrenoceptors do not appear to be involved.

Effects of naloxone on glucose level in the hepatic venous plasma in the rat.

1. The effect of opioid receptor blockade by naloxone in vivo on hepatic venous plasma glucose concentration in rats was investigated. 2. The plasma glucose levels in naloxone-injected animals (10 mg/kg) were higher than in the control animals (P less than 0.05). 3. At the lower dose of naloxone (2 mg/kg) the resulting plasma glucose concentration did not differ significantly from control (P greater than 0.1). 4. It is concluded that endogenous opioids may moderate the regulation of basal glucose levels in the rat.

Correlation of simultaneously determined plasma insulin and glucose levels in fasting and mildly or severely stressed raptors

1. 1. Plasma insulin and glucose levels were simultaneously determined in 60 fasting raptors (seven species) which had experienced mild or severe stress: (1) prolonged confinement in flight cages (Type A), and (2) serious debilities such as fractured bones, soft-tissue damage and/or starvation (Type B) respectively. 2. 2. Two of the species contained Types A and B (43 birds) while the remaining five species (17 birds) were of Type B only. 3. 3. Wide ranges in plasma insulin (0–135 pg/ml or 0–3.0 μU/ml) were observed in both Types A and B. Mean levels were not significantly different between species, although levels in Type B tended to be lower than those in Type A. 4. 4. Wide ranges in plasma glucose (195–485 mg/dl) were also observed in Types A and B but mean levels between species were remarkably similar, and likewise were not significantly different. 5. 5. However, even though mean insulin and glucose levels did not differ significantly between mildly or severely stressed and fasting birds, a low-level but significant ( P < 0.001) correlation ( r = 0.5772) between insulin and glucose levels existed. 6. 6. This suggests that insulin contributes minimally, but significantly, to regulation of plasma glucose levels during stressful experiences or the fasting state.

Semi-Quantitative Measurement of Blood Glucose Levels: An Undergraduate Laboratory Study

Contemporary students seem to enjoy and be stimulated by laboratory studies to which they can relate. This is most likely the reason why courses oriented to human anatomy, physiology, and genetics have popular appeal. On the other hand, introductory laboratory courses directed to the biology major tend to shun exercises in human biology, instead presenting concepts that have applicability to a broad spectrum of organisms. There are, nevertheless, a variety of laboratory studies that, while human oriented, have broad phylogenetic relevance. A good example is the hormonal regulation of glucose levels in blood. The primary hormone involved, insulin, occurs throughout the animal kingdom, including several groups of invertebrates (e.g., mollusks, arthropods, echinoderms, tunicates), and cyclostomes (Falkmer et al. 1973; Macchi and Gapp 1973). Insulin and glucagon also have been shown to be present in cartilagenous and teleost fish, amphibians, reptiles, birds and mammals (Assenmacher 1973; Falkmer and Patent 1972; Falkmer et al. 1975; Norris 1980). Thus, while the pancreatic hormones regulating blood sugar levels have more relevance to humans, their widespread distribution suggests a long and interesting evolutionary history. This paper describes a laboratory study that can be used to provide insights into the pancreatic control of blood glucose levels. It involves an adaptation and modification of a clinical procedure called the glucose tolerance test (Bauer 1982). The data obtained using a modified procedure provide curves that correlate well with those obtained by clinical methodology. General Considerations

Modulation by the nutritional state of adrenergic receptor mediated effects on insulin secretion in ducks.

The effects of exogenous (IV Norepinephrine (NE)) and endogenous alpha adrenergic activity (IV phentolamine (PH)) were studied in the duck. Our aim was first to compare their importance in animals fed for 1 1/2 hours and fasted for 24 and 48 hours, and then to assess the relative importance of alpha versus beta adrenergic receptor mediated effects during the development of a 48-hour-fast. NE reduces plasma IRI levels after a fast but not in the postprandial state. PH while ineffective in animals fed for 1 1/2 hours brings fasting IRI values to levels observed in the former group. Twenty-four hour fasted ducks are sensitive to both alpha adrenergic stimulation and beta adrenergic blockade which have additive effects; so, insulin secretion is controlled by 2 distinct mechanisms: a beta stimulating and an alpha inhibiting one. The importance of one component versus the other is modulated by the nutritional state: indeed, a double alpha and beta equimolar adrenergic blockade reveals that during the transition from the postprandial state to a 48-hour-fast, there is a progressive reversal in the importance of one adrenergic component versus the other. The effects of alpha adrenergic stimulation or blockade occur independently of simultaneous glucose variations. This is not the case for A cell function: an alpha adrenergic receptor stimulating effect on glucagon secretion exists, but A cell remains primarily sensitive to plasma glucose level. alpha Adrenergic activity has no direct effect on plasma free fatty acids (FFA) level but plays a role in plasma glucose level regulation especially in animals in the postprandial state.

Beta adrenergic receptors mediated effects, insulin and plasma free fatty acids in the duck.

Beta-adrenergic blockade by IV propranolol treatment (5 mg/kg), resulted in an important drop in plasma immunoreactive insulin (IRI) in normal 24-hour fasted ducks, indicating that basal insulin secretion is controlled by beta-adrenergic receptors. Concomitantly plasma free fatty acids (FFA) are doubled; this effect is suppressed in animals made insulin-deficient by total pancreatectomy or hypophysectomy and in normal animals when the drop of plasma IRI is prevented by simultaneous administration of insulin. These results show that insulin, considered as devoid of any direct actin on lipolysis in birds, does play a role in plasma FFA regulation in the duck and confirm previous studies on totally pancreatectomized animals. This effect was also observed in fed animals in which propranolol, by decreasing plasma IRI to fasting levels, brings back plasma FFA to values observed in fasted ducks. Furthermore, propranolol, by impairing the hypoglycaemia of hypophysectomized or totally pancreatectomized animals suggest that effects mediated by beta-adrenergic receptors play a direct role in the regulation of plasma glucose level in the duck. Finally, glucose administration in propranolol treated animals show that the beta cell becomes insensitive to glucose in the absence of a normal beta adrenergic stimulation. This is not the case in A cell which remains responsive to hyper- and hypoglycaemia.