Pharmacological Doses Of Glucagon Research Articles

Liraglutide and Dulaglutide Have Comparable HbA1c Reduction in Emirati Patients with T2DM

Glucagon like peptide-1 is responsible for the incretin effect after a meal or an oral glucose load. Patients with type 2 diabetes mellitus have impairment of secretion and action of glucagon like peptide-1. This impairment can be overcome through pharmacological doses of glucagon like peptide-1 analogues. Aim of the Study: This study aimed at evaluation of the effect of treatment with glucagon like peptide-1 analogues; liraglutide and dulaglutide, in Emirati patients with type 2 diabetes mellitus. Glycemic control was the primary end point while the secondary end point was the effect on body mass index, blood pressure, heart rate, serum creatinine, lipid profile and estimated glomerular filtration rate. Patients & Methods: This is a retrospective study including 54 patients with type 2 diabetes mellitus. Patients used Liraglutide or Dulaglutide as add on therapy to oral antidiabetic medications for one year. Thirty-four patients used liraglutide 1.8 mg once daily and 20 patients used dulaglutide 1.5 mg once weekly. All patients were older than 18 years and had estimated glomerular filtration rate (>90 ml/min/1.73 m2). Body mass index, sitting blood pressure and heart rate were collected. Fasting plasma glucose, HbA1c, lipid panel and other biochemical parameters were also collected. Data were analysed before and at 6 and 12 months of glucagon like peptide-1 analogue treatment. Results: At 12 months of treatment, liraglutide significantly reduced fasting plasma glucose (11.3 ± 4 vs 7 ± 1.7, p

The influence of glucagon on the concentration of triacylglycerols and cholesterol in the liver and kidney of mice

Abstract. The experiment was performed on sexually mature male Swiss mice to determine the effect of pharmacological doses of glucagon administered over a period of 4 or 8 days on the concentration of triacylglycerols and cholesterol in liver and kidneys of mice selected for fast rate of body weight gain and unselected ones, kept on a high-protein and low-protein diet. On the basis of the results obtained it was concluded that the selection and the diet, as well as glucagon injections, were lowering the content of triacylglycerols and cholesterol in the examined organs of mice, in many cases confirmed in a statistically significant way.

Ornithine Decarboxylase Induction in Partially Hepatectomized Rat Liver and Modes of Its Stimulation by Glucagon and Insulin

Hepatic ornithine decarboxylase (ODC) activity increases after partial hepatectomy and this activity is further stimulated by pharmacologic doses of glucagon and insulin. We now present data suggesting that glucagon and insulin stimulate ODC activity by distinct mechanisms. ODC activity increased progressively after partial hepatectomy and reached an initial peak at 4 h. Activity decreased to 50% of its peak value at 6 and 8 h and then rose progressively to a maximum at 12 h. Enzymatic activity was well correlated with the amount of hepatic immunoreactive ODC protein, thus suggesting that increased enzyme activity was due to increased amount of enzyme protein. Hepatic ODC mRNA increased gradually and continuously, reaching the maximal value by 12 h. In rats receiving glucagon after partial hepatectomy, ODC mRNA increased significantly by 2 h and enzyme immunoreactive protein and activity by 2 to 4 h as compared to controls. In contrast, insulin administration only induced a significant increase in enzyme immunoreactive protein and activity 10 to 12 h after partial hepatectomy. No significant changes in ODC mRNA level were observed. Our data suggest that the regulation mechanism of ODC induction following partial hepatectomy differs depending on the time after operation. Our data also suggest that while glucagon appears to regulate ODC activity by a transcriptional mechanism, insulin appears to operate at a post-transcriptional level.

Glucagon lowers canine biliary cholesterol output at physiologic doses.

Pharmacologic doses of glucagon affect canine bile secretion by increasing bile flow while simultaneously decreasing biliary cholesterol output. The present study was performed to determine if physiologic doses of glucagon reduce biliary cholesterol output. Awake dogs received both intravenous 1% sodium taurocholate (50 ml/hr) to stabilize bile flow and somatostatin (12 micrograms/kg/hr) to suppress endogenous pancreatic hormone release. Suppression was documented by significant decreases in portal plasma glucagon and insulin levels. During experimental trials, dogs received, in addition, glucagon (5 ng/kg/min) infused via a splenic vein catheter. Bile flow significantly decreased during the initial hour of somatostatin infusion but increased significantly only in experimental trials during subsequent glucagon infusion. Biliary cholesterol output showed no change during control studies (N = 9), but decreased significantly during glucagon infusion studies (N = 11). Biliary phospholipids and bile salts failed to show any changes during glucagon infusion. These data demonstrate that glucagon at physiologic levels influences both the volume and cholesterol content of bile and suggest the mechanism of decreasing cholesterol output must be independent of pathways for influencing bile salt or phospholipid secretion.

Hypoglycemia in the Newborn Growth-Retarded Rat: Delayed Phosphoenolpyruvate Carboxykinase Induction despite Increased Glucagon Availability

We have characterized the sequential changes in plasma glucose, insulin and glucagon concentrations, and hepatic glycogen and phosphoenolpyruvate carboxykinase (PEPCK) during the first 240 min of life in rat pups growth retarded [small for gestational age (SGA)] due to bilateral maternal uterine artery ligation. Pups of sham and nonoperated (normal) mothers served as controls. SGA pups were smaller, had reduced liver mass, and demonstrated a pattern of hypoglycemia. They had significantly reduced plasma glucose concentrations at birth, 20, and 240 min but had normal values at 60 and 120 min. SGA pups had significantly reduced hepatic glycogen stores at birth. Plasma glucagon concentrations in SGA pups increased significantly at 20 and 60 min while insulin concentrations decreased equally in all groups. Hepatic PEPCK activity increased greatly in the sham and normal pups. SGA pups did not induce PEPCK during the first 240 min of life; however, pharmacologic doses of glucagon at birth accelerated PEPCK induction in SGA pups and prevented hypoglycemia. These data indicate that newborn SGA pups develop hypoglycemia because of limited hepatic glycogen stores and retarded gluconeogenesis. The delay in PEPCK induction in SGA pups may result from an inadequate although increased glucagon release at birth or diminished sensitivity to available glucagon.

Effects of glucagon, insulin, propionate, acetate, and HCO3 on K excretion in sheep.

The effects on renal K excretion of 1 h intravenous infusion of glucagon, insulin, Na propionate, Na acetate, or NaHCO3 were studied in mature, conscious fasted ewes. These treatments were compared with the fasted state without treatment (control) and with feeding a single daily meal. Renal K excretion was increased by feeding and by Na propionate and Na acetate treatments but not by infusion of glucagon, insulin, and NaHCO3. Since hormone levels were elevated more by specific hormone infusions than by feeding or Na propionate infusions, these results do not support a role for glucagon and insulin in mediating the increases in renal K excretion that occurred after meals or during acetate and propionate infusions. The mechanisms responsible for the acetate- and propionate-induced kaliuresis are not clear but do not appear to include changes in plasma K (PK), glucagon, and insulin (Pinsulin) or in urine flow and urine Na excretion. However, a relation between insulin and K was observed during infusion of KCl in fasting sheep. Above a PK threshold of 4 meq/l, Pinsulin (ng/ml) = 1.52 PK (meq/l) - 5.89. In other experiments, K excretion increased after an intravenous bolus injection of 1 mg of glucagon, indicating that sheep, like humans and dogs, respond to pharmacologic doses of glucagon with kaliuresis.

The effect of glucagon on the glycosaminoglycan content of canine arteries.

Hypophysectomized young beagles were treated for 21 days with pharmacological doses of glucagon, administered intramuscularly in two daily injections of 0.5 mg each. Hyaluronic acid, heparan, dermatan and isomeric chondroitin sulphates were determined in aorta, carotid, iliac, renal, mesenteric and coronary arteries. In comparison with age-matched hypophysectomized controls, glucagon-treated dogs showed a reduction in the heparan sulphate concentration in their carotid arteries and thoracic aorta. These results indicate that glucagon has a very limited effect on arterial glycosaminoglycan content.

Effect of glucagon on bone collagen metabolism in the rat.

SUMMARY The effect of glucagon on bone was studied in rats. Urinary hydroxyproline excretion and incorporation of [3H]proline into bone hydroxyproline were used as indices of bone collagen breakdown and formation respectively. Parathyroid extract (15 USP units/rat/h, i.v.), infused into thyroparathyroidectomized animals, increased urinary hydroxyproline excretion. This increase was nullified by simultaneous administration of glucagon (50 μg/rat/h, i.v.). Rats treated with glucagon for 12 days (30 μg/100 g/day, s.c.) excreted slightly less hydroxyproline in their urine than controls. In both intact and thyroparathyroidectomized rats, glucagon (10 μg/100 g/h, s.c.) decreased incorporation of [3H]proline into bone. Similar results were obtained in nephrectomized rats, evidence that changes produced by glucagon were not solely due to alterations in proline pool size caused by increased renal excretion. From these data it is concluded that: (1) glucagon can inhibit bone resorption (the effect being slight in normal rats, but easily demonstrable in parathyroid hormone-treated thyroparathyroidectomized rats), (2) release of endogenous calcitonin is not required to produce this effect, (3) parathyroid hormone and glucagon may act on the same target cell in bone, (4) inhibition of skeletal resorption may contribute to glucagon-induced hypocalcaemia, and (5) the hormone possibly decreases bone formation. Since pharmacological doses of glucagon were used in our studies, the relationship of the observations made to the physiological role of glucagon is unknown.

The role of glucagon in cardiac therapy.

Until recently, glucagon has been of primary interest only to the endocrinologist and biochemist. As a polypeptide hormone produced by the alpha cells of the pancreas, its primary physiologic role appears to be related to the maintenance of glucose levels in the blood. Thus, it acts primarily in the liver by activating adenyl cyclase activity, which promotes the formation of cyclic AMP from ATP. Cyclic AMP, in turn, activates phosphorylase and promotes glycogenolysis. Although it has been known for more than a decade that pharmacologic doses of glucagon have cardiovascular actions, it has only been in the last three or . . .

Effects of cortisone and glucagon on rat gestation

It has recently been reported that pharmacologic doses of glucagon given to maternal rats impair fetal growth in utero. Since cortisone administration in pregnancy may sometimes promote a diabetogenic state, the effects of this hormone were compared with those of glucagon. One milligram of cortisone acetate administered twice daily to pregnant rats had little effect on fetal survival. It did, however, modify the effect of glucagon by maintaining maternal weight gain and reducing anorexia. Fetal weight approached normal in litters from mothers treated with both hormones simultaneously. Thus, the effects of these hormones in combination differ from the effect of either hormone alone.

A Comparison of the Effects of Thyrocalcitonin and Glucagon on Plasma Calcium and Phosphate

SummaryThe effect of glucagon has been compared to rat thyrocalcitonin under experimental conditions which had produced information concerning the role of the latter hormone in bone metabolism. The dose-response curve shows that the minimum dose of glucagon needed to produce hypocalcemia produced a dramatic hypophosphatemia and a near-maximum glycogenolytic response. When intact, parathyroidectomized and thyroidectomized rats are treated with pharmacological doses of glucagon, plasma calcium and plasma phosphate changes are similar to those which occur after thyrocalcitonin treatment, thus eliminating the presence of parathyroid and thyroid glands as prerequisite for these effects. Since glucagon is effective in bilaterally nephrectomized animals, these changes can not be due solely to renal effects of the hormone. As with thyrocalcitonin, as the plasma phosphate rises, the hypocalcemic response to glucagon becomes more pronounced. In experiments using either 10-day or 18-hr radiophosphorus labels, glucag...