Intravenous Injection Of Glucagon Research Articles

A Cross-sectional Study to Assess Beta-Cell Function in Individuals with Recently Diagnosed Young-Onset Type 2 Diabetes Mellitus and Its' Complications.

The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications. A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels. 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C-peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C-peptide levels. Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Impact of intravenous injection of glucagon on anastomotic leakage in esophagectomy

BackgroundAnastomotic leakage after esophagectomy affects the early postoperative state and prognosis. However, effective measures to prevent anastomotic leakage in esophagogastric anastomosis have not been established. MethodsThis single-center, retrospective, observational study included 147 patients who underwent esophagectomy for esophageal cancer between 2010 and 2020. Glucagon was administered to extend the gastric tube in patients who underwent esophagectomy from January 2016. The patients were divided into two groups: a glucagon-treated group (2016–2020) and a control group (2010–2015). The incidence of anastomotic leakage was compared between the two groups for evaluation of the preventive effects of glucagon administration on anastomotic leakage. ResultsThe length of the gastric tube from the pyloric ring to the final branch of the right gastroepiploic artery was extended by 2.8 cm after glucagon injection. The incidence of anastomotic leakage was significantly lower in the glucagon-treated group (19% vs. 38%; p = 0.014). Multivariate analysis showed that glucagon injection was the only independent factor associated with a reduction in anastomotic leakage (odds ratio, 0.26; 95% confidence interval, 0.07–0.87). Esophagogastric anastomosis was performed proximal to the final branch of the right gastroepiploic artery in 37% patients in the glucagon-treated group, and these cases showed a lower incidence of anastomotic leakage than did those with anastomosis distal to the final branch of the right gastroepiploic artery (10% vs. 25%, p = 0.087). ConclusionsExtension of the gastric tube by intravenous glucagon administration during gastric mobilization in esophagectomy for esophageal cancer may be effective in preventing anastomotic leakage.

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

High-resolution Mapping of Hyperglycemia-induced Gastric Slow Wave Dysrhythmias.

Background/AimsIt is now recognised that gastric dysrhythmias are best characterised by their spatial propagation pattern. Hyperglycemia is an important cause of gastric slow wave dysrhythmia, however, the spatiotemporal patterns of dysrhythmias in this context have not been investigated. This study aims to investigate the relationship between hyperglycemia and the patterns of dysrhythmias by employing high-resolution (multi-electrode) mapping simultaneously at the anterior and posterior gastric serosa.MethodsHigh-resolution mapping (8 × 16 electrodes per serosal) was performed in 4 anesthetized hounds. Baseline recordings (21 ± 8 minutes) were followed by intravenous injection of glucagon (0.5 mg per dose) and further recordings (59 ± 15 minutes). Blood glucose levels were monitored manually using a glucose sensing kit at regular 5-minute intervals. Slow wave activation maps, amplitudes, velocity, anisotropic ratio, and frequency were calculated. Differences were compared between baseline and post glucagon injection.ResultsBaseline slow waves propagated symmetrically and antegrade. The blood glucose levels were increased by an average of 112% compared to the baseline by the end of the recordings. All subjects demonstrated elevated incidence of slow wave dysrhythmias following injection compared to the baseline (48 ± 23% vs 6 ± 4%, P < 0.05). Dysrhythmias arose simultaneously or independently on anterior and posterior serosa. Spatial dysrhythmias occurred before and persisted after the onset and disappearance of temporal dysrhythmias.ConclusionsInfusion of glucagon induced gastric slow wave dysrhythmias, which occurred across a heterogeneous range of patterns and frequencies. The spatial dysrhythmias of gastric slow waves were shown to be more prevalent and persisted over a longer period of time compared to the temporal dysrhythmias.

Same Hormone, Different Actions

Glucagon signaling in the hypothalamus limits hepatic glucose production, rather than stimulating glucose production as this hormone does in the liver.

Hypothalamic glucagon signaling inhibits hepatic glucose production

Glucagon activates hepatic protein kinase A (PKA) to increase glucose production, but the gluco-stimulatory effect is transient even in the presence of continuous intravenous glucagon infusion. Continuous intravenous infusion of insulin, however, inhibits glucose production through its sustained actions in both the liver and the mediobasal hypothalamus (MBH). In a pancreatic clamp setting, MBH infusion with glucagon activated MBH PKA and inhibited hepatic glucose production (HGP) in rats, as did central glucagon infusion in mice. Inhibition of glucagon receptor-PKA signaling in the MBH and hepatic vagotomy each negated the effect of MBH glucagon in rats, whereas the central effect of glucagon was diminished in glucagon receptor knockout mice. A sustained rise in plasma glucagon concentrations transiently increased HGP, and this transiency was abolished in rats with negated MBH glucagon action. In a nonclamp setting, MBH glucagon infusion improved glucose tolerance, and inhibition of glucagon receptor-PKA signaling in the MBH enhanced the ability of intravenous glucagon injection to increase plasma glucose concentrations. We also detected a similar enhancement of glucose concentrations that was associated with a disruption in MBH glucagon signaling in rats fed a high-fat diet. We show that hypothalamic glucagon signaling inhibits HGP and suggest that hypothalamic glucagon resistance contributes to hyperglycemia in diabetes and obesity.

Clinical, immunologic and insulin secretory characteristics of young black South African patients with diabetes: Hospital based single centre study

AimsTo classify and characterize the clinical features of various diabetes classes among young black South Africans. MethodsCross sectional study of 60 black patients with diabetes, all less than 30 years of age and attending Nelson Mandela Academic Hospital, Mthatha, South Africa. Diabetes was classified as Types 1A, 1B and 2 based on the anti-glutamic acid decarboxylase status and serum C-peptide response to intravenous injection of glucagon. ResultsMean age was 19.6±4.8 years (n=60) with similar gender distribution. The mean duration of diabetes was 24.2±45.1 months. Type 1A was the class of diabetes in 55% (n=33/60) of patients. Type 1B and 2 accounted for 30% (n=18/60) and 15% (n=9/60) of patients respectively. Patients classified as Type 2 had higher waist circumference and higher prevalence of acanthosis nigricans than Types 1A and 1B groups. History of diabetes in a first degree relative and hypertension were found in similar proportions of patients with Types 1A, 1B and 2 diabetes. Five Type 1A diabetes patients had body mass index of 26.2–41kg/m2 and this included two newly diagnosed patients with body mass index of 26.7kg/m2 and 33.2kg/m2. ConclusionThe majority of our young black South Africans with diabetes are of the Type 1A class. Acanthosis nigricans was not found in any patient with Type 1 A diabetes. A minority of Type 1 A diabetes patients were obese at initial diagnosis.

Utility of indices using C-peptide levels for indication of insulin therapy to achieve good glycemic control in Japanese patients with type 2 diabetes.

Aims/Introduction: Type 2 diabetes is progressive in that therapy must be altered over time, which is partly as a result of the progressive loss of pancreatic β-cell function. To elucidate the relationship between residual endogenous insulin secretion and the necessity of insulin therapy to achieve good glycemic control, indices using serum C-peptide immunoreactivity (CPR) were analyzed in patients with type 2 diabetes. The data of 201 Japanese patients with type 2 diabetes who achieved the target of glycemic control during admission were analyzed retrospectively. Indices using CPR including fasting CPR (FCPR), CPR 6 min after intravenous injection of glucagon (CPR-6 min), increment of CPR (ΔCPR), secretory unit of islet in transplantation index (SUIT) and C-peptide index (CPI) were compared between the group requiring insulin (insulin group) and the group not requiring insulin (non-insulin group). A receiver-operator characteristic (ROC) curve was made, and optimal cut-off point and likelihood ratio were determined for each index. All indices of CPR were lower in the insulin group compared with those in the non-insulin group. Likelihood ratios at the optimal point of FCPR, CPR-6 min, ΔCPR, SUIT, and CPI were 2.0, 2.1, 1.6, 2.3 and 2.8, respectively. Optimal cut-off point of CPI was 1.1 ng/mg. Sensitivity and specificity at optimal point of CPI were 61 and 78%, respectively. The advantage of CPI of the indices of CPR to select insulin therapy to achieve good glycemic control was shown, but limitations of the predictive abilities of the indices using CPR should be taken into account. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00096.x, 2011).

Response of one-humped camel (Camelus dromedarius) to intravenous glucagon injection and to infusion of glucose and volatile fatty acids, and the kinetics of glucagon disappearance from the blood.

The effects of glucagon injection and infusion of glucose and volatile fatty acids were studied in one-humped camels. Twenty adult male camels were divided into four equal groups. The first group was infused with physiological saline and served as a control. The second group was injected with a single dose of glucagon, the third group was infused with glucose (50%) in sterile saline, and the fourth group was infused with a volatile fatty acid (VFA) mixture. In the first, third and fourth groups, sampling was performed before the beginning of infusions (control time), and at 15, 30, 60 and 120 min post-infusion. Plasma glucagon concentrations were monitored in the second group at 5, 10, 15, 20, 30, 45, 90, 105 and 120 min after injection. For glucagon injection, glucose concentration peaked at 15 min post-injection, and tended to decrease thereafter. Plasma glucose concentrations showed significant rises above the basal value at all times after glucose infusion. VFA infusion had no apparent effect on plasma glucose concentration. After injection of glucagon, the plasma lactate concentration dropped significantly at 15 and 30 min, then increased gradually until it reached the original concentration of lactate at 120 min. However, glucose infusion elevated the plasma lactate concentration only at the end of the infusion period. A decrease in plasma lactate was observed at 60 min after VFA infusion. The present investigation provides evidence that the glucagon level in camels is higher than that in other ruminants and in man, and suggests that this is a probable species specificity, which would explain the higher level of glucose in the blood of camels than in that of other ruminants. The disappearance curve of injected glucagon had, as in other ruminants, an exponential two-compartment function. The hormone was rapidly distributed and was eliminated with a high rate of clearance.

Section of the vagal celiac branch in man reduces glucagon-stimulated insulin release

The purpose of this study was to determine whether section of the celiac branch of the vagus nerve in man affects the insulin response to intravenous glucagon injection. Patients who received a subtotal gastrectomy with lymph node dissection for gastric carcinoma were divided into two groups: the celiac-preserved group ( n=16) and the celiac-sectioned group ( n=13). The hepatic branches of the vagus were preserved in both groups. The glucagon test was performed twice in each patient during the operation; before and after manipulation of the celiac branch. Blood samples were collected just before and 6 min after the injection. No difference in the mean increases in blood glucose, insulin and C-peptide levels were seen between the two groups before the nerve manipulation. In the celiac-preserved group, the glucagon stimulated glucose-related C-peptide ratio (×10 −3) was 0.5±0.7 before the nerve manipulation and 3.5±3.0 after it, a significant difference ( p<0.01). In the celiac-sectioned group, this increase was not observed, the ratio was 0.7±0.6 before the nerve manipulation and 0.8±3.4 after. These results indicate that the vagal celiac branch in man may also be involved in the control of pancreatic insulin release.

Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus

We examined the response of plasma islet amyloid polypeptide (IAPP) to an oral glucose load in non-obese and obese subjects with normal glucose tolerance or impaired glucose tolerance (IGT), and in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma IAPP response to intravenous glucagon injection in NIDDM patients was also studied. Plasma IAPP concentration was determined by a sensitive and specific radioimmunoassay. Basal levels of plasma IAPP in non-obese subjects with normal glucose tolerance, IGT and NIDDM were not significantly different from each other. Non-obese subjects with IGT showed delayed and higher plasma IAPP response to oral glucose load compared to normal non-obese subjects. In NIDDM patients, IAPP response to glucose was delayed and lower when compared to normal non-obese subjects. Basal levels of plasma IAPP in normal obese subjects and obese subjects with IGT were significantly higher than those in normal non-obese subjects. Plasma IAPP response to glucose load in these obese subjects was higher than that in normal non-obese subjects. Plasma IAPP response was decreased in diabetic patients treated with diet, oral hypoglycemic agents and insulin in that order. We conclude that the secretion of IAPP is reduced with progression of NIDDM, although it appears to be rather augmented in IGT compared to normal non-obese subjects.

Remission In Diabetic Children In Riyadh

Few data are available about temporary remission in insulin dependent mellitus in Riyadh. Thirty-seven out of 115 (32.1%) diabetic children diagnosed over five and a half years (1985 to mid-1990) in Suleimania Children's Hospital were retrospectively studied. Partial temporary remission rate was 30.4% (35/115). Total temporary remission rate was 1.7% (2/115), lasting 18 months in a seven-year-old patient. The partial remission rate was higher in children above five years of age (36.9%), in children of unrelated parents (34.3%) and in female patients (51.4%). Of these, 64.8% were Saudi. Fifty-four percent of these patients presentd at onset without diabetic ketoacidosis and mean duration of symptoms before diagnosis was short (9.2 days). Mean time of occurrence was five weeks and mean duration of remission was nine weeks. Mean initial insulin dose was 1.35 unit/kg/day, while mean dose during the remission was 0.34 unit/kg/day. Mean glycosylated hemoglobin at onset was 12.3% and 7.4% during remission. Mean C-peptide level improved markedly from 0.16 nmol/L at onset to 0.29 nmol/L during remission and rose to 0.61 nmol/L following glucagon intravenous injection demonstrating the temporary recovery of pancreatic B-cell function. Finally, our low figures of remission (32.1%) are probably related to the young age distribution at onset in our series and perhaps to a different pattern of severity of insulin dependent diabetes mellitus in our community.

Urinary C-peptide as an index of unstable glycemic control in insulin-dependent diabetes mellitus (IDDM)

In order to investigate whether urinary C-peptide (UCP) excretion can be a useful index of insulin-dependent diabetes mellitus (IDDM) with unstable glycemic control, UCP was measured in nine IDDM patients with unstable glycemic control, nine IDDM patients with stable glycemic control, and 12 non-insulin-dependent diabetic (NIDDM) patients treated with insulin. The UCPs in overnight urine (U1) and fasting single void urine (U2) in IDDM patients with unstable glycemic control were significantly lower than those in IDDM patients with stable glycemic control (U1: 0.03 ± 0.03 vs 0.24 ± 0.20 nmol/mmol-Creatinine, U2: 0.02 ± 0.01 vs 0.20 ± 0.20 nmol/mmol-Cr, mean ± SD, both P < 0.01). The UCPs in U1 and U2 in both groups of IDDM were significantly lower than those in NIDDM (U1: 0.97 ± 0.52, U2: 0.73 ± 0.41 nmol/mmol-Cr, both P < 0.01). The UCPs in U1 and U2 significantly correlated with incremental C-peptide response to intravenous glucagon injection and with glycemic stability assessed by the standard deviation of 10 previous fasting plasma glucose levels. These results suggest that UCP reflects their residual insulin secretory capacity and that UCP can be a useful index which distinguishes patients with unstable IDDM from those with stable diabetes mellitus.

Partial structure and hormonal regulation of rabbit liver inhibitor-1; distribution of inhibitor-1 and inhibitor-2 in rabbit and rat tissues

Inhibitor-1 purified from rabbit liver could not be distinguished from the skeletal muscle protein by chromatographic, electrophoretic and immunological criteria. Amino acid sequences comprising 68% of rabbit liver inhibitor-1 were identical to the skeletal muscle protein indicating that they are products of a single gene. Total inhibitor-1 activity in heat-treated rabbit liver extracts was similar to that in skeletal muscle extracts, and the phosphorylation state of inhibitor-1 increased from 14% to 42% in rabbit liver in vivo after an intravenous injection of glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-1 recognised a single major protein of identical electrophoretic mobility (26 kDa) in each rabbit tissue examined (skeletal muscle, liver, brain, heart, kidney, uterus and adipose). The antibodies also recognised a single major (30 kDa) protein in the same rat tissues, except liver. The results show that while there are interspecies differences in apparent molecular mass, inhibitor-1 is likely to be the same gene product in each mammalian tissue. Inhibitor-1 was not detected in rat liver, either by activity measurements or immunoblotting, irrespective of the age, sex or strain of the animals. Immunoblotting also failed to detect inhibitor-1 in mouse liver, although it was present in guinea pig, porcine and sheep liver. The absence of inhibitor-1 in rat liver indicates that phosphorylation of this protein cannot underlie the increased phosphorylation of hydroxymethylglutaryl-CoA reductase observed after stimulation by glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-2 recognised a 31 kDa protein in each rabbit tissue, and a 33 kDa protein in all rat tissues including liver. The results suggest that inhibitor-2 is the same gene product in each mammalian tissue.

Effect of Somatotropin and Dietary Protein Concentration on Hormone and Metabolite Responses to Single Injections of Hormones and Glucose

Four lactating Holstein cows averaging 155 d postpartum were used in a crossover design to examine the influence of somatotropin administration (33 mg/d for 28 d) and dietary CP (11 vs. 16% CP) concentration on physiological responses to single intravenous injections of glucagon, insulin, glucose, and somatotropin. Dietary CP was without influence on plasma hormone or metabolite responses to the challenges but increased basal concentrations of FFA. Basal concentrations of glucagon, glucose, and insulin were not significantly increased by somatotropin treatment; however, there was a tendency for insulin concentrations to be higher in somatotropin-treated cows. Somatotropin treatment increased basal concentrations of somatotropin and FFA. Increases in glucose concentrations after glucagon challenge occurred more quickly, reached a greater peak, and lasted longer for cows treated with somatotropin than for control cows. Insulin concentrations were decreased after somatotropin challenge in control cows, but not in somatotropin-treated cows. Responses of metabolites and hormones to glucose or somatotropin challenges were not influenced by somatotropin treatment. Changes in the metabolism of glucose and insulin suggest that cows treated with somatotropin have a greater ability to synthesize and conserve glucose than control cows. Data obtained support the concept of the homeorhetic action of somatotropin.

Evidence for increased sympatho-adrenomedullary activity in young subjects with borderline hypertension.

Three different studies were performed to estimate the sympatho-adrenomedullary activity in young subjects with borderline hypertension (BHT, n = 40), compared with age-matched normotensive subjects (NT, n = 24). In the first study, 23 BHT and 9 NT were subjected to isometric stress by maintaining handgrip at the 30% level of maximal voluntary contraction for 3 min. The response of plasma total catecholamines at the second and third min during the isometric exercise were greater in BHT than in NT (98.9 +/- 24.3 vs. 18.0 +/- 30.7 and 93.0 +/- 12.6 vs. 47.1 +/- 15.4 pg/ml, respectively, p less than 0.05). In the second study, the effects of intravenous glucagon injection (1 USP unit) were studied in 12 BHT and 9 NT. The increments of plasma epinephrine (E) at 2 and 3 min after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4 pg/ml, and 68.9 +/- 13.2 vs 32.1 +/- 8.9 pg/ml, respectively, p less than 0.05. In the last study, the pressor effects of intravenous norepinephrine (NE) infusion (100 and 200 ng/kg/min for 15 min) were examined in 17 BHT and 15 NT under three different sodium balances: regular customary diet, treatment with diuretics and high-sodium diet. Treatment with diuretics decreased and high-sodium diet increased the pressor response to NE in both groups, but there were no significant differences in NE reactivity between 2 groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of starvation and treatment of rats with anti-insulin serum, glucagon and catecholamines on the state of phosphorylation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in vivo.

The fraction of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in the dephosphorylated (active) form in rat liver in vivo was measured after various experimental treatments of animals. Intraperitoneal injection of glucose (to raise serum insulin concentrations) into rats 4 h into the light phase (L-4) resulted in a transient (30 min) increase in the expressed (E)/total (T) activity ratio of HMG-CoA reductase without any change in total activity (obtained after complete dephosphorylation of the enzyme). Conversely, intravenous injection of guinea-pig anti-insulin serum into rats 4 h into the dark phase (D-4) significantly depressed the E/T ratio within 20 min. Intravenous injection of glucagon into normal rats at this time point did not affect the degree of phosphorylation of the enzyme, in spite of a 10-fold increase in hepatic cyclic AMP concentration induced by the hormone treatment. A 3-fold increase in the concentration of the cyclic nucleotide induced by adrenaline infusion was similarly ineffective in inducing any change in expressed or total activities of hepatic HMG-CoA reductase. However, when insulin secretion was inhibited, either by the induction of streptozotocin-diabetes or by simultaneous infusion of somatostatin, glucagon treatment was able to depress the expressed activity of HMG-CoA reductase (i.e. it increased the phosphorylation of the enzyme). Therefore insulin appears to have a dominant role in the regulation of the phosphorylation state of hepatic HMG-CoA reductase. In apparent corroboration of this suggestion, short-term 4 h food deprivation of animals before D-4 resulted in a marked decrease in the E/T activity ratio of reductase, which was not affected further by an additional 8 h starvation. By contrast, the total activity of the enzyme was not significantly affected by 4 h starvation, but was markedly diminished after 12 or 24 h starvation. Longer-term starvation also produced a chronic increase in the degree of phosphorylation of the enzyme. These results are discussed in relation to the role of reversible phosphorylation in the control of hepatic HMG-CoA reductase activity in vivo.

Increased sympatho-adrenomedullary activity in young patients with borderline hypertension: hyperresponses to isometric stress and glucagon injection

The purpose of this study was to estimate the sympatho-adrenomedullary activity in young patients with borderline hypertension (BHT, n=23), compared with age-matched normotensive subjects (NT, n=9), so that two studies were performed as follows: they were subjected to isometric stress, by maintaining handgrip at the 30% level of maximal voluntary contraction for three minutes. With the exercise blood pressure and pulse rate increased to the same degree in BHT as in NT. In contrast, the response of plasma total catecholamine (plasma epinephrine plus norepinephrine) at the end of this isometric exercise was greater in BHT than in NT (93.0 +/- 12.6 in BHT vs. 47.1 +/- 15.4pg/ml in NT). Moreover, the effects of intravenous glucagon injection (1 USP unit) were studied in twelve subjects of BHT (n = 12) and all of NT (n = 9). The injection of glucagon induced a transient increase in pulse rate, but there was no significant difference in the elevation of pulse rate with glucagon between BHT and NT. Plasma epinephrine also increased temporarily, and returned to the baseline within ten minutes after injection. The increments of plasma epinephrine at two and three minutes after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4pg/ml, and 68.9 +/- 13.2 vs. 32.1 +/- 8.9 pg/ml, respectively. Thus, patients with borderline hypertension had the augmented response of plasma catecholamine to both isometric exercise and glucagon stimulation. Evidence presented suggests that the responses of sympathetic nervous system and adrenal medulla to stress are increased in young patients with borderline hypertension. Moreover, the augmented response of sympatho-adrenomedullary system to stress may be involved in the development of essential hypertension.

Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated perfused right atria.

In an isolated right atrial preparation, which was cross-perfused with heparinized arterial blood from a support dog, we investigated the effects of glucagon on heart rate and systemic arterial blood pressure of the support dog and on atrial rate and contractile force of the isolated perfused atrium when glucagon was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrial preparation. Glucagon (0.3 to 3 micrograms/Kg i.v.) to the support dog dose-dependently induced a prominent increase in heart rate and a small increase in systemic arterial blood pressure. In the isolated, perfused atrium, marked positive chronotropic and slight, but significant, positive inotropic effects were evoked dose-dependently 1.5 min after intravenous injection of glucagon. These positive effects were not altered significantly by propranolol (1 mg/Kg i.v.). Direct injection of glucagon into the sinus node artery of isolated atria also induced marked positive chronotropic and small positive inotropic effects dose-dependently. CF/HR ratios, inotropic effect per chronotropic effect in isolated atria, of glucagon injected intravenously or intraarterially were less than 0.7 and they were much less than those of norepinephrine (more than 3.6). These results confirm that glucagon injected intravenously or regionally produces a prominent positive chronotropic effect and a small positive inotropic effect and suggest that glucagon may be less effective as a cardiotonic agent.