Effects of the amylin analogue pramlintide on hepatic glucagon responses and intermediary metabolism in Type 1 diabetic subjects

Aims Hepatic glycogen stores have been shown to be depleted, and

 production reduced, in Type 1 diabetic subjects.

Neonatal blood glucose concentrations: metabolic effects of intravenous glucagon and intragastric medium chain triglyceride.

 administration exerted a glycaemic effect which was associated with an increase in 

Metabolic response to glucose ingested with various amounts of protein.

 resulted in a decrease in alpha-amino nitrogen and 

 concentrations whereas ingestion of protein increased them as expected.

Intranasal Glucagon as Remedy for Hypoglycemia: Studies in Healthy Subjects and Type I Diabetic Patients

The effect of protein ingestion on the metabolic response to oral glucose in normal individuals.

 to the protein meal resulted in a 60 min delay in 

 and AAN rise compared to the protein meal alone.

Cortisol, glucagon and growth hormone responses to oral glucose in non-insulin-dependent diabetes in the young.

 was only significantly suppressed 150 minutes after 

 loading in the NIDDY group, in contrast to the reference group, which showed maximum suppression at 90 minutes; at all time intervals plasma glucagon levels were significantly higher in the NIDDY patients.

Metabolic adaptations in post-exercise recovery.

 was given (+48 +/- 13 pg ml-1) and at the end of the OGTT.

The effects of glucagon on protein metabolism in normal man.

 (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml).

Insulin, Free Fatty Acids, and Glucose Response to Intravenous Glucagon Following Myocardial Infarction

Optimization of Truncated Glucagon Peptides to Achieve Selective, High Potency, Full Antagonists.

 biological action is a proven strategy for decreasing 

Lactate activation of α-cell KATP channels inhibits glucagon secretion by hyperpolarizing the membrane potential and reducing Ca2+ entry

 secretion, how lactate and pyruvate control α-cell Ca2+ handling is unknown.

The role of α-cells in islet function and glucose homeostasis in health and type 2 diabetes.

 seems also required for an optimal insulin secretion in response to 

 by acting on its cognate receptor and, even more importantly, on GLP-1 receptors.

A Primary Role for α-Cells as Amino Acid Sensors

 output, and hyperglucagonemia is partly responsible for the hyperglycemia in diabetes, making glucagon an attractive target for therapeutic intervention.

Glucagon regulates hepatic mitochondrial function and biogenesis through FOXO1.

 production maintaining glucose homeostasis in the fasting state.

Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation

Glucagon and Amino Acids Are Linked in a Mutual Feedback Cycle: The Liver–α-Cell Axis

 is important for minute-to-minute regulation of postprandial 

 production, although conditions of glucagon excess or deficiency do not cause changes compatible with this view.

Physiological and pathophysiological aspects of incretin hormones and glucagon.

 used in that particular study was more than 15-fold higher than ours and associated with large changes in 

Glucagon is the key factor in the development of diabetes

 and ketone production, the catabolic features of insulin deficiency.

Diabetes: New treatment approach for T1DM

In the first experiment, in which a normal hamster cell line was used, increasing the concentration of

 were three times higher when the mice had abnormally high levels of 

 than after the insulin injection (when levels of glucose were normal).

Recent progress in the development of small-molecule glucagon receptor antagonists.

 output via its action at the glucagon receptor (GCGr) in the liver.

Glucose regulation of glucagon secretion.

 secretion that tend to balance and even exceed the inhibitory influence.

Growth factor signalling in the regulation of α‐cell fate

 homeostasis, mainly by counteracting the effects of insulin.

The role of dysregulated glucagon secretion in type 2 diabetes

 production and abnormal glucose homeostasis.

Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis

Glucose generates coincident insulin and somatostatin pulses and antisynchronous glucagon pulses from human pancreatic islets.

 from 3 to 20 mm resulted in a brief pulse of 

 coinciding with suppression of basal insulin and somatostatin release.

Pulsatility of insulin release – a clinically important phenomenon

Studies of hormone secretion from the perfused pancreas of rats and mice revealed that

 anti-synchronous with pulses of insulin and somatostatin.

GLP-1 receptors in golden syrian hamster islets

 concentration decreased by 46 ± 4% the release of 

, but GLP-1 failed to exert any obvious effect on glucagon secretion in the presence of 8.3 mMd-glucose.

Glucagon and glucagon-like peptide receptors as drug targets.

 production, taken together with data from studies employing glucagon antagonists, glucagon receptor antisense oligonucleotides, and glucagon receptor knockout mice, suggest that reducing glucagon action may be a useful strategy for the treatment of type 2 diabetes.

Characterization of a novel Foxa (hepatocyte nuclear factor-3) site in the glucagon promoter that is conserved between rodents and humans.

 production and thus maintains blood glucose levels in the fasting state.

The Gly40Ser Mutation in the Human Glucagon Receptor Gene Associated With NIDDM Results in a Receptor With Reduced Sensitivity to Glucagon

 production and has also been shown to potentiate glucose-induced insulin secretion.

[Current data on insulin secretion and its regulation].

 too; it is difficult to distinguish between its endocrine and paracrine role.

Unresponsiveness to Glucose in a Streptozocin Model of Diabetes: Inappropriate Insulin and Glucagon Responses to a Reduction of Glucose Concentration

 release in the controls, but had no effect in the STZ rats.

Glucoregulation and simulated diving in the harbor seal Phoca vitulina.

Physiology of glucagon.

 is important in the physiological regulation of 

An important role for glucagon in the regulation of glucose production in vivo.

In postabsorptive insulin-dependent diabetic man, a

 infusion at 5 ng/kg/min is associated with a prompt rise in 

 production followed by a return to basal production despite continued glucagon infusion.

Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.

 immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent.

Effect of intravenously administered glucose on glucagon and insulin secretion during fat absorption.

 was found to alter profoundly the response of insulin and 

 to an intraduodenally administered fat meal in conscious dogs from that of dogs given only intravenous saline as a control.

Glucagon physiology and pathophysiology.

THE function of pancreatic glucagon has been questioned for several decades, but it now seems probable that

, like insulin, is extremely important in the moment-to-moment control of the homeostasis of 

, of certain amino acids and perhaps of free fatty acids.

Diazoxide in von Gierke's disease.

More recent attempts to modify the course of this disease have involved the use of thyroxine (Koulischer and Pickering, 1956) and

 (Lowe et al., 1959) to influence the intermediary metabolism of 

Glucagonostatic Potency of GLP-1 in Patients With Type 2 Diabetes, Patients With Type 1 Diabetes, and Healthy Control Subjects

 secretion may contribute to the hyperglucagonemia in diabetes and influence the success of GLP-1 receptor agonist therapy.

Efficacy of Dose-Titrated Glucagon Infusions in the Management of Congenital Hyperinsulinism: A Case Series

By releasing intrahepatic glucose stores,

Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver

 production, lipolysis and amino acid catabolism.

Cell Autonomous Dysfunction and Insulin Resistance in Pancreatic α Cells

 production and blood glucose levels, paradoxical glucagon hypersecretion is observed in diabetes.

Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes

During OGTT, glucose levels rose less and glucagon levels fell more in DS vs D.   Conclusion The degree of

 and insulin secretion and to lipid mobilization during short-term SGLT2 inhibition.

[Glucagon antagonists open a new way in treatment of type 2 diabetes Mellitus].

 in diabetic animals resulted in decreased 

 production, reduction of fasting and prandial hyperglycemia, and improved glucose tolerance.

Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study

 during cycling was diminished by a pre-exercise injection of 200 μg 

; however, no significant difference was seen in the number of events of hypoglycaemia.

Rebirth of the Incretin Concept: Its conception and early development

The concept evolved with the discovery by Samols and co‐workers that

 stimulated the release of immunoreactive 

 from the gut mucosa and the subsequent isolation of glucagon immunoreactive compounds, most notably oxyntomodulin and glicentin, and of gastic inhibitory polypetide (GIP).

On the role of the gut in diabetic hyperglucagonaemia.

 production, and, thus, the elevated glucagon concentrations in diabetes contribute decisively to the predominating trait of patients with diabetes namely hyperglycaemia.

Concurrent insulinoma and impaired glucose tolerance suspected as owing to obesity

Despite the prolonged fast, the glucose response to

Higher Endogenous Glucose Production During OGTT vs Isoglycemic Intravenous Glucose Infusion.

 ingestion elicits a larger insulin response and delayed suppression of 

 compared to isoglycemic IV glucose infusion (IIGI).

Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes

Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study

Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the

Islet α cells and glucagon—critical regulators of energy homeostasis

 is secreted from islet α cells and controls blood levels of 

Comment on Kramer et al. Glucagon Response to Oral Glucose Challenge in Type 1 Diabetes: Lack of Impact of Euglycemia. Diabetes Care 2014;37:1076–1082

 may be one of the significant causes of hyperglycemia in patients with type 1 diabetes, its results should be carefully interpreted …

Glucagon Response to Oral Glucose Challenge in Type 1 Diabetes: Lack of Impact of Euglycemia

CONCLUSIONS In patients with T1D, there is a paradoxical increase in

 that is not reversed when euglycemia is achieved prior to the test.

Assessment of glycemic response to an oral glucokinase activator in a proof of concept study: application of a semi-mechanistic, integrated glucose-insulin-glucagon model

 production in the model was increased by 

 and glucagon production was inhibited by elevated glucose concentrations.

Diabetic ketoacidosis as a rare complication of electromyography and nerve conduction velocity examination.

Dipeptidyl Peptidase-4 Inhibitors in the Elderly: More Benefits or Risks?

These hormones potentiate the acute effects of

 on pancreatic alfa and beta cells, thus stimulating insulin secretion, and only GLP-1 inhibits 

 secretion in a glucose-dependent manner (that is, only when glucose levels are increased); as a result, they reduce hyperglycemia with virtually no hypoglycemic risk.

Glucagon and cyclic AMP: time to turn the page?

 can stimulate adipose lipolysis, myocardial contractility, and 

 output by activating a GPCR and adenylate cyclase (AC) and increasing cAMP production.

[Incretin hormones].

GLP-1 receptors have been proved in liver recently but decreased

 production and increased glucose uptake by liver and muscle are mediated indirectly by altering insulin and 

Factors Influencing the Effectiveness of Glucagon for Preventing Hypoglycemia

 was significantly lower in failures versus successes (86 ± 3 versus 95 ± 3 mg/dl, p = .04).

Insulinoma in a patient with normal results from prolonged fast and glucagon-induced hypoglycemia.

 from 50 to 18 mg/dL, elevations in insulin and C-peptide, and suppression of β-hydroxybutyrate.

Impaired glucose-induced glucagon suppression after partial pancreatectomy.

 concentrations before surgery (P < 0.0001), but this was lost after partial pancreatectomy (P < 0.01 vs. preoperative values).

Monitoring laboratory values: glucose, hemoglobin, hematocrit, and iron.

Islet Cell Dysfunction in Progression to Diabetes Mellitus

In addition, new therapeutic modalities need to address alpha-cell dysregulation, because the inability to suppress

 production results in ongoing elevated levels of 

In addition, new therapeutic modalities need to address α-cell dysregulation, because the inability to suppress

The regulation of insulin and glucagon secretion by opiates: A study with naloxone in healthy humans

 concentration was less pronounced during naloxone.

Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus

Conclusions/interpretationAttenuated and delayed

 suppression in patients with type 2 diabetes occurs after oral ingestion of 

Nutritional Considerations in Wound Care

 from amino acids, ultimately resulting in a reduced storage of glucose, fatty acids, and proteins.

Pancreatic secretion in man with subclinical vitamin D deficiency

 was partly restored after vitamin D supplementation in epileptic patients but not in geriatric patients.

Avoiding hypoglycaemia when treating type 1 diabetes

Counterregulation involves a series of defensive physiological … that are triggered in response to a

, including release of anti-insulin hormones such as 

, adrenaline, noradrenaline, growth hormone and cortisol (and the switching off of insulin secretion in nondiabetics) together with stimulation of the autonomic nervous system [3].

B cell function in patients with chronic pancreatitis and its relation to exocrine pancreatic function

 was closely correlated (r = 0.88,p < 0.01).

Glucagon secretion in relation to insulin sensitivity in healthy subjects

Conclusions/interpretationThe body adapts to insulin resistance by increasing the glucagon response to arginine and by increasing the suppression of

The acute glucagon response (AGR) to arginine during the three glucose levels (AGR1, AGR2, AGR3) was estimated, as was the suppression of baseline

Glucose production rates in type 1 glycogen storage disease

 rate as well as blood glucose and lactate concentrations.

Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis.

 and insulin concentrations were matched and 

 concentrations were suppressed, both glycogenolysis and gluconeogenesis were higher (P < 0.01) in the diabetic versus the obese and lean nondiabetic subjects.

Previous exposure to glucose enhances insulin and suppresses glucagon responses to argentine in man

Conclusions: (1) a near-physiological intake of

 secretion evoked by amino acids resulting in increased glucose disposal; (2) the modifications of the insulin and glucagon responses constitute separate components in the feed-back regulation of glucose homeostasis.

Where's the protein?

Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-l-diabetic patients after successful combined pancreas and kidney transplantation

Decreased hepatic glucagon responses in Type 1 (insulin-dependent) diabetes mellitus

 at a physiologic plasma concentration diabetic patients had 1) an overall reduced 

 production response and 2) an abnormal sluggish response pattern.

Effects of muscarinic blockade on the thermic effect of oral or intravenous carbohydrate

 concentrations, with or without atropine, were both decreased to 201 (SEM 18) μmol·l−1 and 74 (SEM 4) ng·l−1, respectively, after 2 h of 

, and were not further suppressed after oral fructose.

Factors affecting E-rosette forming ability in peripheral lymphocytes of insulin dependent diabetics

Incubation of lymphocytes from a subsequent … insulin (100 μU/ml) plus

 (100 mg/100 ml) significantly increased E-rosette ….0±2.2; p= 0.01); conversely 

 (0.1 μg/ml) significantly impaired E-rosette forming ability of … vs 44.5±4.2; n=17; p< 0.01).

Plasma glucagon and glucagon-like immunoreactive components in Type 1 (insulin-dependent) diabetic patients and normal subjects before and after an oral glucose load

 in diabetic patients may be due to an increase of both IRG3500 and/or IRG9000, (2) the gut-glucagon-like immunoreactivity released during …-glucagonlike immunoreactivity were observed in Type 1 diabetic patients when compared with normal subjects, either in the basal state or after glucose ingestion.

Postprandial GLP-1, Norepinephrine, and Reactive Hypoglycemia in Dumping Syndrome

Early immunoreactivities of GLP-1, GIP, and

 and were significantly higher in dumpers.

The gastro-entero-pancreatic hormone response to fasting in obesity

, secretin and vaso-active intestinal polypeptide.

Treatment issues in type 1 diabetes.

Comparing the effects of first-phase and second-phase insulin release in response to

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