128-LB: Effects of Glucagon Receptor Antagonism (GRA) on Ketone Body Formation during Insulinopenia in Type 1 Diabetes (T1D)

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 128-LB
Author(s):  
SCHAFER C. BOEDER ◽  
DANIEL G. INES ◽  
LESLIE CARTER ◽  
ERIN R. GIOVANNETTI ◽  
DEBRA ARMSTRONG ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Ketone Body ◽  
Glucagon Receptor ◽  
Receptor Antagonism ◽  
Body Formation

scholarly journals Glucagon Receptor Knockout Prevents Insulin-Deficient Type 1 Diabetes in Mice

Diabetes ◽  
2011 ◽  
Vol 60 (2) ◽  
pp. 391-397 ◽  
Author(s):  
Y. Lee ◽  
M.-Y. Wang ◽  
X. Q. Du ◽  
M. J. Charron ◽  
R. H. Unger
Keyword(s):  
Type 1 Diabetes ◽  
Glucagon Receptor ◽  
Diabetes In Mice

scholarly journals Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway

2015 ◽  
Vol 112 (8) ◽  
pp. 2503-2508 ◽  
Author(s):  
May-Yun Wang ◽  
Hai Yan ◽  
Zhiqing Shi ◽  
Matthew R. Evans ◽  
Xinxin Yu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Insulin Treatment ◽  
Glucagon Secretion ◽  
Glucagon Receptor ◽  
Acute Increase ◽  
Deficient Mice ◽  
Hba1c Levels

Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D. Mice with T1D receiving insulin treatment paradoxically exhibited threefold higher plasma glucagon during hyperglycemic surges than during normoglycemic intervals. Blockade of glucagon action with mAb Ac, a glucagon receptor (GCGR) antagonizing antibody, maintained glucose below 100 mg/dL and HbA1c levels below 4% in insulin-deficient mice with T1D. In rodents with T1D, hyperglycemia stimulates glucagon secretion, up-regulating phosphoenolpyruvate carboxykinase and enhancing hyperglycemia. GCGR antagonism in mice with T1D normalizes glucose and HbA1c, even without insulin.

Hepatic Glucagon Receptor In Rats: Effect Of Type 1 Diabetes.

2008 ◽  
Vol 32 (4) ◽  
pp. 352
Author(s):  
Johnatan Lamanque ◽  
Jessica Morissette ◽  
Alexandre Melançon ◽  
Geneviève Robert ◽  
François Péronnet ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucagon Receptor

scholarly journals AVP-induced counter-regulatory glucagon is diminished in type 1 diabetes

2020 ◽  
Author(s):  
Angela Kim ◽  
Jakob G. Knudsen ◽  
Joseph C. Madara ◽  
Anna Benrick ◽  
Thomas Hill ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucagon Secretion ◽  
Human Islets ◽  
Alpha Cells ◽  
Glucagon Receptor ◽  
Major Barrier ◽  
Neuron Activation ◽  
Circulating Levels

AbstractHypoglycaemia is a major barrier to the treatment of diabetes. Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon – the body’s principle blood glucose-elevating hormone which is secreted from alpha-cells of the pancreatic islets. In isolated islets, varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (from 8 to 4 mM) has no significant effect on glucagon secretion and yet associates with dramatic changes in plasma glucagon in vivo. The identity of the systemic factor that stimulates glucagon secretion in vivo remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Glucagon-secreting alpha-cells express high levels of the vasopressin 1b receptor (V1bR). Activation of AVP neurons in vivo increased circulating AVP, stimulated glucagon release and evoked hyperglycaemia; effects blocked by pharmacological antagonism of either the glucagon receptor or vasopressin 1b receptor. AVP also mediates the stimulatory effects of dehydration and hypoglycaemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata, which are known to be activated by hypoglycaemia, drive AVP neuron activation in response to insulin-induced hypoglycaemia. Hypoglycaemia also increases circulating levels of copeptin (derived from the same pre-pro hormone as AVP) levels in humans and this hormone stimulates glucagon secretion from isolated human islets. In patients with type 1 diabetes, hypoglycaemia failed to increase both plasma copeptin and glucagon. These findings provide a new mechanism for the central regulation of glucagon secretion in both health and disease.

scholarly journals Effect of a glucagon receptor antibody (REMD‐477) in type 1 diabetes: A randomized controlled trial

2018 ◽  
Vol 20 (5) ◽  
pp. 1302-1305 ◽  
Author(s):  
Jeremy Pettus ◽  
Dominic Reeds ◽  
Tricia S. Cavaiola ◽  
Schafer Boeder ◽  
Michelle Levin ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Type 1 Diabetes ◽  
Controlled Trial ◽  
Glucagon Receptor ◽  
Receptor Antibody ◽  
Randomized Controlled

236-OR: Volagidemab, a Human Glucagon Receptor Antagonist, Improves Glycemic Control in Subjects with Type 1 Diabetes (T1D): A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 236-OR
Author(s):  
JEREMY PETTUS ◽  
SCHAFER C. BOEDER ◽  
MARK P. CHRISTIANSEN ◽  
DOUGLAS S. DENHAM ◽  
TIMOTHY S. BAILEY ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Receptor Antagonist ◽  
Controlled Trial ◽  
Double Blind ◽  
Glucagon Receptor ◽  
Double Blind Placebo ◽  
Glucagon Receptor Antagonist
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