Effects Of Glucagon Administration Research Articles

Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 +/- 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography-mass spectrometry following constant rate infusion of [6,6-(2)H2]glucose and [2-(13)C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed. Plasma glucose and glycerol averaged 3.8 +/- 0.5 mmol/L and 384 +/- 183 micromol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 +/- 2.9 micromol/kg per min. Mean rate of glucose production was 30.2 +/- 4.6 micromol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% +/- 19%, beta-cell function to 221% +/- 73%, and insulin resistance to 1.3 +/- 0.3. After glucagon administration, rate of glucose production increased by 13.3 +/- 8.3 micromol/kg per min and blood glucose by 1.4 +/- 0.5 mmol/L. Glycerol production decreased from 12.8 +/- 3.0 to 10.7 +/- 2.9 micromol/kg per min. Mean insulin concentration increased from 10.9 +/- 3.0 to 30.9 +/- 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

Effects of glucagon administration on the microcirculation, hemorheology and hemostasis

Effects of glucagon administration on the microcirculation, hemorheology and hemostasis

The effect of glucagon administration on protein synthesis in skeletal muscles, heart and liver in vivo.

Infusion of glucagon (0.5 mg/h per 100 g body wt.) into fed rats for 6 h inhibited protein synthesis in skeletal muscle, but not in heart. The order of sensitivity of three muscles was plantaris greater than gastrocnemius greater than soleus. Treatment with glucagon for periods of 1 h or less had no effect. Liver protein synthesis was inhibited by glucagon treatment for 10 min, but stimulated after 6 h. The effect of glucagon on muscle was not secondary to impaired food absorption or to depletion of amino acids by increased gluconeogenesis, since the inhibition of protein synthesis was observed in postabsorptive and amino acid-infused rats. The failure of glucagon to inhibit muscle protein synthesis after 1 h may have been caused by the increase in plasma insulin that occurred at this time, since an inhibition was detected in insulin-treated diabetic rats. The lowest infusion rate that gave a significant decrease in muscle protein synthesis was 6 micrograms/h per 100 g body wt., despite a small increase in plasma insulin. This gave plasma glucagon concentrations in the high pathophysiological range, suggesting that glucagon may be significant in the pathogenesis of muscle wasting in metabolic stresses such as diabetes and starvation.

Interrelation between somatostatin output from the mediobasal hypothalamus and plasma growth hormone levels in conscious rats: effects of glucagon administration.

The interrelationship between SRIF output from the mediobasal hypothalamus and plasma GH levels was studied in conscious male rats using the push-pull perfusion technique in combination with repeated blood samplings. The MBH was perfused with artificial cerebrospinal fluid at the rate of 30 microliter/min, and blood samples were collected every 20 min from 1000-1700 h. In control animals, which received injection of acidified saline at 1100 h into the lateral ventricle, two large episodes of spontaneous GH secretion occurred regularly at around 1200 and 1540 h, and troughs occurred around 1400 h. In contrast, SRIF levels from mediobasal hypothalamus perfusate fluctuated at random, ranging from 10-116 pg/ml, with a mean value of 39.2 pg/ml. Mean SRIF levels at 1200 and 1540 h (43.4 +/- 9.0 and 24.4 +/- 4.2 pg/ml, respectively; n = 8) were not different from those at 1400 h (39.9 +/- 12.2 pg/ml). When glucagon (10 micrograms/rat) was injected at 1100 h, plasma GH levels decreased and remained low until 1600 h, whereas perfusate SRIF levels were elevated and remained high for the period. In these animals, the mean plasma GH levels during 1120-1540 h were lower than those in control rats [17.2 +/- 2.4 ng/ml (n = 9) vs. 143.4 +/- 17.5 ng/ml (n = 8); P less than 0.01]. In contrast, the mean SRIF levels in glucagon-treated rats were higher than those in controls [112.5 +/- 15.9 pg/ml (n = 9) vs. control 40.1 +/- 4.3 pg/ml (n = 8); P less than 0.01]. These results suggest that SRIF plays a role in tonic inhibition of GH release in response to the intracerebroventricular injection of glucagon in conscious rats, although SRIF plays, if any, a minor role in regulating episodic GH secretion.

Effects of insulin and glucagon on plasma glucose levels and glycogen content in organs of the freshwater teleost Pimelodus maculatus

Mammalian insulin (350 IU/kg) and glucagon (2.5 mg/kg) were injected intraperitoneally into Pimelodus maculatus, a South American teleost. Extent of carbohydrate regulation was estimated through determination of plasma glucose levels, liver-somatic index, and liver and muscle glycogen contents. The effects of insulin administration, examined 6, 12, 24, 48, and 72 hr after injection, were manifested as a depletion of liver glycogen content after 12 hr and severe decrease in plasma glucose content after 24 hr; insulin had no effect on muscle glycogen or liver-somatic index. The effects of glucagon administration, examined 5, 15, 30, 90, and 360 min after injection, were a small increase in liver glycogen content after 15 min, and hyperglycemia, apparent after 30 min. Glucagon did not affect muscle glycogen or liver-somatic index. Control animals were injected intraperitoneally with saline solution. These results suggest that insulin and glucagon regulate the carbohydrate metabolism of P. maculatus by hormonal mechanisms similar to those operating in other teleost species and in mammals.

Effect of glucagon administration on kidney morphology in house shrew, Suncus murinus.

Effect of glucagon administration on kidney morphology in house shrew, Suncus murinus.

Effect of glucagon administration on mice liver fructose-1, 6-bisphosphatase

Intravenous administration of glucagon in mouse (200 μg/100 gm body wt), stimulated liver fructose-1,6-bisphosphatase at physiological pH by approximately 100% within 15 minutes. The stimulation was not due to protein synthesis. Similar stimulation was also observed on administration of cyclic AMP. Removal of the adrenal gland abolished the stimulatory effect of glucagon but not of cyclic AMP.

Plasma immunoreactive somatostatin levels in rat hypophysial portal blood: Effect of glucagon administration

Plasma somatostatin levels of the hypophysial portal blood was examined in urethane-anesthetized rats. Portal blood was withdrawn at a rate of 4.7 μl/min via a cannula placed over the stump of the pituitary stalk, collected into the ice-cold tube at 20min intervals before and after the intraventricular injection of test materials. Immunoreactive somatostatin extracted from the plasma with acid acetone was measured by a specific radioimmunoassay. Basal plasma somatostatin concentrations, 778±52pg/ml (means±SE), did not significantly change after the administration of control solution (0.1N acetic acid in physiological saline), while intraventricular injection of glucagon (2, 10 and 50 μg) caused a significant and dose-related increase in plasma somatostatin during the first 20min. These results suggested that somatostatin release from the median eminence into the hypophysial portal vessel was stimulated by glucagon, although the physiologycal significance remains to be clarified.

Glucagon and plasma lipoprotein lipase.

SummarySubcutaneous administration of 1.0 mg glucagon to 15 fasted normal people caused significant increase of plasma lipoprotein lipase-like activity in 1 hr. The activity is termed lipase-like since coconut oil emulsion rather than isolated chylomicrons was used as substrate. A linear relationship between lipolysis and time of incubation obtained indicating zero order kinetics. pH optimum of enzyme activity was 8.4. There was no correlation between depression of plasma triglycerides and increase -of plasma lipoprotein lipase-like activity following glucagon administration. This was thought to be due to other effects of glucagon administration which alter plasma lipid levels. Incubation of whole blood with glucagon caused an increase of plasma lipoprotein lipase-like activity and a depression of plasma triglycerides that were significantly correlated. The in vitro action of glucagon when incubated with whole blood suggests that blood cell(s) may be a source of glucagon-induced plasma lipoprotein lipase ...

Effect of glucagon, insulin and acetylcholine on heart glycogen synthetase and phosphorylase activity

The effect of glucagon administration on the heart glycogen synthetase and phosphorylase systems in control and insulin-pretreated rats has been studied. A rapid decrease in percent synthetase I activity was found in both control and insulin-pretreated animals after glucagon administration. This was associated with a simultaneous increase in percent phosphorylase a. Propranolol did not block the response. The results are compatible with a mechanism in which protein kinase is activated by increased cyclic AMP concentration which affects both the synthetase and phosphorylase systems simultaneously. The response of the synthetase and phosphorylase systems to glucagon was little affected by insulin; glycogen breakdown, however, was blocked completely. The mechanism of this is entirely unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vitro. Acetylcholine alone had no effect, nor did it modify the response of the synthetase and phosphorylase systems to either insulin or glucagon. However, it did produce a slight inhibition in percent phosphorylase a increase after glucagon.

Responses of mammalian histidine catabolic enzymes to dietary and hormonal treatments

1. 1. The effects of glucagon administration on hepatic histidase, urocanase, and histidine-pyruvate aminotransferase activities in vivo and interrelationships among a high protein intake, cortisol and glucagon in influencing the activities of these enzymes were studied. Histidine-pyruvate aminotransferase increased 30-fold in rats fed a 12% casein diet and injected subcutaneously with glucagon for 10 days, whereas histidase and urocanase increased only 3-fold and 2-fold, respectively. After withdrawal of glucagon, the aminotransferase decreased with an apparent half-life of 3.5 days. Kinetic analysis indicated that an increased rate of enzyme synthesis was responsible for the increases in enzymic activities. 2. 2. Histidine-pyruvate aminotransferase is also more responsive than histidase and urocanase in rats injected with cortisol and responded synergistically when glucagon and cortisol were administered together. The aminotransferase shows little response in rats fed a high protein diet. In contrast, histidase and urocanase are more responsive than the aminotransferase to induction by high protein feeding but respond only moderately in rats treated with cortisol or glucagon. Glucagon treatment seems to enhance the induction of histidase or urocanase by high protein feeding but the effect is less than additive.

Effects of Glucagon and Insulin on Gastric Secretion in Rats

Zollinger and Ellison 1 suggested in 1955 that noninsulin-secreting islet cell tumors of the pancreas are associated with atypical peptic ulcer and gastric hypersecretion. The possibility was considered that the islet cell factor involved might be related to the secretion of glucagon by the tumor. Al­ though bioassay studies have not demon­ strated an increased glucagon content in the islet cell tumor, the question of a stimulating effect of glucagon on gastric secretion re­ mains open because of the possibility of associated metabolic changes. These might be responsible for a rise in available gluca­ gon, either by increasing its formation from extrapancreatic sources or by decreasing its inactivation. A change in the sensitivity threshold to a circulating hormone should also be considered before the association between pancreatic islet cell tumor, de­ rangement of gastric secretory mechanism and atypical ulceration is discarded. Apart from its possible role in the Zollin­ ger-Ellison syndrome, the effects of glucagon administration on gastric secretion pose several interesting problems in gastric physi­ ology. Several modifying factors appear to be operational in gastric secretory response to glucagon, including the possibility of its dependence upon levels of circulating cate­ chol amines and inhibition of histamine­ induced stimulation. Some studies on the effects of insulin on gastric secretion have also been included in our report, because of certain similarities in the response to that of glucagon.

Electron microscopy of the rat pancreas; effects of glucagon administration.

Electron microscopy of the rat pancreas; effects of glucagon administration.