Regulation of plasma immunoreactive glucagon in obese hyperglycaemic (ob/ob) mice

1982 ◽  
Vol 95 (2) ◽  
pp. 215-227 ◽  
Author(s):  
P. R. Flatt ◽  
C. J. Bailey ◽  
K. D. Buchanan
Keyword(s):  
Cell Function ◽  
Glucagon Secretion ◽  
Plasma Glucagon ◽  
Fasted State ◽  
A Cell ◽  
Old Mice ◽  
Noradrenaline And Adrenaline ◽  
Adrenaline Administration ◽  
Suppressive Action

This study examines the role of glucagon in the pathogenesis of the obese hyperglycaemic (ob/ob) syndrome in mice. Plasma C-terminal immunoreactive glucagon concentrations were measured in fed and fasted ob/ob mice at different ages between 5–40 weeks, and in 20-week-old mice after the administration of established stimulators and inhibitors of glucagon secretion. Plasma glucagon concentrations were inappropriately raised irrespective of age, nutritional status and the accompanying prominent changes in plasma glucose and insulin concentrations. Glucose suppressed plasma glucagon in the fed but not the fasted state, suggesting a dependence on the marked hyperinsulinaemia associated with feeding. Administration of 0·25 units insulin/kg to fasted mice failed to affect plasma glucagon and glucose concentrations. Increasing the dose to 100 units/kg restored the normal suppressive actions of insulin. Fasted mice showed an exaggerated glucagon response to arginine but not to the parasympathomimetic agent pilocarpine. Fed mice displayed normal plasma glucagon responses to the sympathomimetic agents noradrenaline and adrenaline. Administration of insulin antiserum or 2-deoxy-l-glucose raised plasma glucagon concentrations of fed mice. Contrary to the lack of suppression by glucose in the fasted state, heparin-induced increase in free fatty acids reduced plasma glucagon concentrations. This study demonstrates inappropriate hyperglucagonaemia and defective A-cell function in ob/ob mice. The extent of the abnormality is exacerbated by fasting and appears to result from insensitivity of the A-cell to the normal suppressive action of insulin.

Plasma glucagon, glucose, and free fatty acid concentrations and secretion during prolonged hypothermia in rats

1991 ◽  
Vol 260 (3) ◽  
pp. R480-R485 ◽  
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
C. Moreau-Hansany ◽  
L. C. Wang
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Beta Cell Function ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Plasma Glucagon ◽  
Tissue Sensitivity ◽  
Pancreatic Alpha Cell ◽  
Alpha Cell Function

Impairment of metabolic substrate mobilization and utilization may be a factor limiting survival in hypothermia. Using a newly developed technique for maintaining stable low body temperature (Tb), substrate profiles and their regulation by glucagon were examined in hypothermic rats (Tb 19 +/- 0.3 degrees C) over 20 h. During cooling, plasma glucagon, glucose, and free fatty acid (FFA) concentrations increased significantly (536 +/- 55 pg/ml, 304 +/- 26 mg/100 ml, and 844 +/- 81 mueq/l, respectively). Plasma glucagon and glucose concentrations continued to increase up to 8 h (peaks 810 +/- 103 pg/ml and 451 +/- 33 mg/100 ml, respectively) and remained high throughout the rest of the hypothermic period. FFA concentrations decreased steadily during the hypothermic period. Exogenous glucagon (20 micrograms/kg) induced significant increases in plasma glucose (+129 +/- 31 mg/100 ml) and FFA concentrations (+351 mueq/l) at 2 h but had no effect at 15 h of hypothermia. In vitro evaluation of pancreatic alpha-cell function indicated that glucagon secretion is independent of temperature between 37 and 19 degrees C. Our data indicate that hypothermia is characterized by a disturbed substrate metabolism, which is likely due to an imbalance in pancreatic alpha- and beta-cell function and a time-dependent decrease in tissue sensitivity to glucagon. These deleterious changes may limit survival in hypothermia.

Alcam Mediated Interaction Regulates Normal Hematopoietic Stem Cell Function and Cbfβ-SMMHC Induced Leukemogenesis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4091-4091
Author(s):  
Robin Jeannet ◽  
Qi Cai ◽  
Hongjun Liu ◽  
Hieu Vu ◽  
Ya-Huei Kuo
Keyword(s):  
Fusion Protein ◽  
Cell Function ◽  
Conflicts Of Interest ◽  
Immunoglobulin Superfamily ◽  
Leukemic Transformation ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
A Cell

Abstract Abstract 4091 The inv(16) acute myeloid leukemia (AML)-associated CBFβ-SMMHC fusion protein impairs hematopoietic differentiation and predisposes to leukemic transformation. Alcam, which encodes the activated leukocyte cell adhesion molecule (CD166), is a cell surface immunoglobulin superfamily member mediating homophilic adhesion as well as heterotypic interactions with CD6. We found that Alcam expression marks long-term repopulating HSCs (LT-HSC), multipotent progenitors (MPP), a subset of granulocyte-macrophage progenitors (GMP), and that Alcam expression is lost or reduced in subsets of pre-leukemic and leukemic progenitors expressing the Cbfβ-SMMHC fusion protein. We characterized the role of Alcam in HSC differentiation and self-renewal using an Alcam-null (Alcam−/−) mouse model (Weiner et al. 2004 Mol Cell Neurosci 27:1, 59–69). We show that Alcam is highly expressed in LT-HSCs where its level progressively increases with age. Young adult Alcam−/− mice had normal homeostatic hematopoiesis, and normal numbers of phenotypic HSCs. However, Alcam−/− HSCs had reduced long-term replating capacity in vitro and reduced long-term engraftment potential upon transplantation. We show that Alcam−/− BM contain a markedly lower frequency of long-term repopulating cells than wild type (WT). Further, the long-term repopulating potential and engraftment efficiency of Alcam−/− LT-HSCs was greatly compromised despite a progressive increase in phenotypic LT-HSC numbers during long-term serial transplantation. In addition, an age-associated increase in phenotypic LT-HSC cellularity was observed in Alcam−/− mice. This increase was predominately within the CD150hi fraction, and was accompanied by significantly reduced leukocyte output. Moreover, Alcam−/− LT-HSCs display premature elevation of Selp expression, a hallmark of HSC aging. To understand the role of Alcam in leukemic transformation, we generated conditional Cbfb-MYH11 knock-in (Cbfb56M/+/Mx1-Cre), Alcam-deficient (Alcam−/−) mice. Interestingly, we found that loss of Alcam drastically delayed or reduced leukemia incidence. Transplantation of Alcam−/−/Cbfb56M/+/Mx1-Cre pre-leukemic bone marrow cells into WT recipients also led to delayed and reduced incidence of leukemia development. These results suggest that Alcam contributes to leukemia transformation in a cell-intrinsic manner. Collectively, our study reveals that Alcam regulates the functional integrity and self-renewal of LT-HSCs, and contributes to leukemia initiation induced by CBFβ-SMMHC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Puddu ◽  
François Mach ◽  
Alessio Nencioni ◽  
Giorgio Luciano Viviani ◽  
Fabrizio Montecucco
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Advanced Glycation ◽  
Chronic Hyperglycemia ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreaticβ-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

scholarly journals Reduced somatostatin signalling leads to hypersecretion of glucagon in mice fed a high fat diet

2020 ◽  
Author(s):  
Joely A. Kellard ◽  
Nils J. G. Rorsman ◽  
Thomas G. Hill ◽  
Sarah L Armour ◽  
Martijn van der Bunt ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Experimental Models ◽  
Alpha Cell ◽  
Isolated Islets ◽  
Alpha Cells ◽  
Plasma Glucagon ◽  
High Fat

AbstractElevated plasma glucagon is an early symptom of diabetes, occurring in subjects with impaired glucose regulation. Here we explored alpha-cell function in female mice fed a high fat diet (HFD) – a widely used mouse model of pre-diabetes. In vivo, HFD-fed mice have increased fed plasma glucagon levels that are unaffected by elevation of plasma glucose. To explore the underlying mechanisms, we conducted experiments on isolated islets and in the perfused pancreas. In both experimental models, glucagon secretion under both hypo- and hyperglycaemic conditions was elevated. Because Ca2+ is an important intracellular regulator of glucagon release in alpha-cells, we fed mice expressing the Ca2+ indicator GCaMP3 specifically in alpha-cells the HFD. In mice fed a control (CTL) diet, increasing glucose reduced intracellular Ca2+ ([Ca2+]i) (oscillation frequency and amplitude). This effect was not observed in HFD mice where both the frequency and amplitude of the [Ca2+]i oscillations were higher than in CTL alpha-cells. Given that alpha-cells are under strong paracrine control from neighbouring somatostatin-secreting delta-cells, we hypothesised that this elevation of alpha-cell output was due to a lack of somatostatin (SST) secretion. Indeed, SST secretion in isolated islets from HFD mice was reduced but exogenous SST also failed to suppress glucagon secretion and Ca2+ activity from HFD alpha-cells, in contrast to observations in CTL mice. These findings suggest that reduced delta-cell function, combined with intrinsic changes in alpha-cell sensitivity to somatostatin, accounts for the hyperglucagonaemia in mice fed a HFD.

Role of Wnt/PCP pathway on bronchial cell function in Idiopathic Pulmonary Fibrosis

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
S Barkha ◽  
M Gegg ◽  
H Lickert ◽  
M Königshoff
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Function

The Role of GLP-1 Receptor Expressed in Pancreatic a Cells in Regulating Glucagon Secretion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 355-OR ◽  
Author(s):  
YANQING ZHANG ◽  
KESHAB R. PARAJULI ◽  
GENEVIEVE E. SMITH ◽  
RAJESH GUPTA ◽  
WEIWEI XU ◽  
...  
Keyword(s):  
Glucagon Secretion ◽  
A Cells

STIM1/Orai1 Inhibition Reduces Store-Operated Ca2+Entry and Modulates a-Cell Glucagon Secretion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2174-P
Author(s):  
MOLLY K. ALTMAN ◽  
PRASANNA DADI ◽  
DAVID JACOBSON
Keyword(s):  
Glucagon Secretion ◽  
A Cell

Study of Possible Relation between Fasting Plasma Glucagon, Gestational Diabetes and Development of Type 2 DM

2020 ◽  
Vol 16 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Ashraf Okba ◽  
Salwa Seddik Hosny ◽  
Alyaa Elsherbeny ◽  
Manal Mohsin Kamal
Keyword(s):  
Gestational Diabetes ◽  
Pregnant Women ◽  
Post Partum ◽  
Plasma Glucagon ◽  
Type 2 Dm ◽  
Fasting Plasma ◽  
Before And After ◽  
Two Phases

Background and Aims: Women who develop GDM (gestational diabetes mellitus) have a relative insulin secretion deficiency, the severity of which may be predictive for later development of diabetes. This study aimed to investigate the role of fasting plasma glucagon in the prediction of later development of diabetes in pregnant women with GDM. Materials and Methods: The study was conducted on 150 pregnant women with GDM after giving informed oral and written consents and being approved by the research ethical committee according to the declaration of Helsinki. The study was conducted in two phases, first phase during pregnancy and the second one was 6 months post-partum, as we measured fasting plasma glucagon before and after delivery together with fasting and 2 hour post-prandial plasma sugar. Results: Our findings suggested that glucagon levels significantly increased after delivery in the majority 14/25 (56%) of GDM women who developed type 2 DM within 6 months after delivery compared to 6/20 (30%) patients with impaired fasting plasma glucose (IFG) and only 22/105 (20%) non DM women, as the median glucagon levels were 80,76, 55, respectively. Also, there was a high statistical difference between fasting plasma glucagon post-delivery among diabetic and non-diabetic women (p ≤ 0.001). These results indicated the useful role of assessing fasting plasma glucagon before and after delivery in patients with GDM to predict the possibility of type 2 DM. Conclusion: There is a relatively high glucagon level in GDM patients, which is a significant pathogenic factor in the incidence of subsequent diabetes in women with a history of GDM. This could be important in the design of follow-up programs for women with previous GDM.

Sign in / Sign up

Export Citation Format

Share Document