Glucagon Administration Research Articles

Experience with intravenous glucagon infusions as a treatment for resistant neonatal hypoglycemia.

Based on limited anecdotal evidence, glucagon is used for the management of intractable neonatal hypoglycemia persisting in the face of high glucose administration rates. To evaluate the short-term response of blood glucose levels to an intravenous infusion of glucagon. A retrospective observational study in which all newborns who received glucagon infusions (usual dose, 0.5-1 mg/d) during a 5-year period were identified (N = 55). The common causes of hypoglycemia were perinatal stress, intrauterine growth restriction, prematurity, and maternal diabetes mellitus. Laboratory blood glucose measurements made between 24 hours before and 72 hours after the start of the glucagon infusion and the rates of glucose administration during the same period were analyzed. The effects of glucagon on sodium and platelet levels were also examined. University referral hospital. A statistically and clinically significant rise in blood glucose concentration, from a mean of 36.3 to 93.0 mg/dL (2.02-5.17 mmol/L), was observed within 4 hours of starting glucagon administration. The change was unrelated to the cause of the hypoglycemia. The frequency of hypoglycemic episodes was significantly reduced, and no further episodes of severe hypoglycemia (glucose level, <20 mg/dL [<1.1 mmol/L]) occurred. Five patients, 4 of whom were preterm newborns with intrauterine growth restriction, required additional glycemic treatment. Seventy-five percent of newborns were thrombocytopenic before starting glucagon infusion, and in 9 newborns platelet counts decreased following glucagon infusion. There was no hyponatremia attributable to glucagon. Glucagon infusions appear to be beneficial for problematic neonatal hypoglycemia of different causes.

Neonatal Care of the Infant of the Diabetic Mother

After completing this article, readers should be able to: 1. Describe the most significant factor influencing neonatal morbidity in the diabetic pregnancy. 2. Characterize the impact of maintaining as normal a metabolic state as possible on the potential for perinatal and neonatal complications. 3. Describe the optimal location and services for delivery of a diabetic parturient. 4. Characterize the evaluation of an infant of a diabetic mother who requires resuscitation after birth. 5. Delineate the factor that most increases the chance of successful management of an infant of a diabetic mother in a regular nursery setting. Although many infants of diabetic mothers (IDMs) have an uneventful perinatal course, there is still an increased risk of complications, even in the infant born to the woman who has gestational diabetes. This discussion highlights specific factors that are critical in the immediate care of the IDM in the delivery room, in the nursery, and after discharge from the hospital. The care of this neonate builds on the pathophysiologic concepts presented in “The Infant of the Diabetic Mother” also appearing in this issue and other recent reviews of the subject. (1)(2) The physician responsible for the care and delivery of the parturient must inform the neonatologist, pediatrician, or their designee responsible for the care of the neonate of the mother’s condition well in advance of delivery to ensure optimal care of the newborn. Among the specific factors that are of utmost importance are the type of diabetes and degree of maternal control, prior pregnancy history, and complications occurring during the pregnancy, including data about fetal monitoring for determination of fetal size and maturation. This information allows the physician caring for the neonate to anticipate many, if not most, of the potential fetal and neonatal complications and assist in determining if a neonatologist needs to be present …

Paroxysmal supraventricular tachycardia after administration of glucagon during upper endoscopy

Paroxysmal supraventricular tachycardia after administration of glucagon during upper endoscopy

Paroxysmal supraventricular tachycardia after administration of glucagon during upper endoscopy

Paroxysmal supraventricular tachycardia after administration of glucagon during upper endoscopy

Glucagon administration elicits blunted GH but exaggerated ACTH response in obesity

Reduction in both spontaneous and stimulated GH secretion in obesity has been clearly demonstrated. Mild hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis has been also reported. Glucagon, at least after im administration, induces clear increase in either GH or ACTH and F levels but its effect on somatotroph and corticotroph secretion in obesity has never been studied. In 7 patients with abdominal obesity (OB, aged 24-42 yr, BMI: 29.1-43.9 kg/m2, waist/hip ratio [WHR]: 0.86-1.00) we studied the GH, ACTH and F responses to the im administration of glucagon (0.017 mg/kg at 0 min). The results in OB were compared with those in a group of 6 age-matched controls normal subjects (Ns aged 26-32 yr, BMI 19.7-22.5 kg/m2). In Ns glucagon administration induced clear increase in GH (peak vs baseline, mean+/-SE: 11.6+/-3.4 vs 3.3+/-0.7 microg/l, p<0.02), and ACTH (52.9+/-15.2 vs 19.0+/-1.5 pg/ml, p<0.02) levels which peaked at +150 and +165 min, respectively. Increase in F levels (222.3+/-23.8 vs 158.3+/-7.0 ng/ml, p<0.05) was also recorded but peaked at +180 min. In OB glucagon administration induced GH response (7.4+/-2.3 vs 0.8+/-0.6 microg/l) lower (p<0.05) than that recorded in Ns; when the GH responses were evaluated by co-variance analysis, a significant difference between the 2 groups was recorded in term of peaks but not of AUCs. On the other hand, the ACTH response to glucagon in OB was higher than that in Ns (11452.6+/-2447.7 vs 4892.2+/-719.4 pg/ml x min, p<0.05). The F response to glucagon in OB and Ns was, however, similar (24057.9+/-4109.1 vs 29835.9+/-1566.0 ng/ml x min). In conclusion, this study demonstrates that in obese patients the im administration of glucagon elicits blunted GH response but exaggerated ACTH increase which is uncoupled with the adrenal response. These findings agree with the existence of concomitant GH insufficiency and altered corticotroph function in obesity.

Calcium and Beta Receptor Antagonist Overdose: A Review and Update of Pharmacological Principles and Management

Calcium channel and beta-adrenergic receptor antagonists are common pharmaceutical agents with multiple overlapping clinical indications. When used appropriately, these agents are safe and efficacious. In overdose, however, these agents have the potential for serious morbidity. Calcium channel blockers and beta blockers share similar physiological effects on the cardiovascular system, such as hypotension and bradycardia, in overdose and occasionally at therapeutic doses. The initial management for symptomatic overdose of both drug classes consists of supportive care measures. Other therapies including administration of glucagon, calcium, catecholamines, phosphodiesterase inhibitors and insulin have been used with varying degrees of success. In addition, intra-aortic balloon pump and extracorporeal membrane oxygenation techniques have been successfully utilized in refractory cases. This article reviews beta blocker and calcium channel blocker pharmacological principles and updates current management strategies.

CT colonography: colonic distention improved by dual positioning but not intravenous glucagon

The aim of this study was to determine whether intravenous (IV) glucagon and dual positioning administered prior to CT colonography enhances colonic distention. We assessed the effect of dual positioning and IV glucagon on colonic distention in 96 patients who underwent CT colonography examinations. The CT colonography was performed in both supine and prone positions. Seventy-four patients received glucagon (1 mg i.v.) immediately prior to CT scanning and 22 patients did not. The bowel was divided into ten segments and colonic distention was scored by two radiologists in the supine, prone, and combined supine/prone positions using a five-point scale: 1=collapsed; 2=poorly visualized; > or = 3=adequate distention; 4=entire segment visualized and well distended; 5=excellent distention). A combined segmental and overall supine/prone distention score was calculated based on the sum of the mean score for each position. There was no significant difference in the degree of colonic distention between patients who received glucagon and those who did not [supine/prone distention score (mean +/- SE): 3.63 +/- 0.2 vs 3.85 +/- 0.2; p=n.s.]. The degree of colonic distention was greater in the prone position in both the glucagon (3.87 +/- 0.2 vs 3.38 +/- 0.2; p<0.05) and non-glucagon groups (4.01 +/- 0.2 vs 3.69 +/- 0.2; p=N.S.) particularly in the proximal colon. There was almost perfect agreement between both radiologists in their scoring of colonic distention on a per-patient basis ( k=0.9; p<0.001). Of 1480 bowel segments, 1261 (85.2%) were adequately distended in the glucagon group compared with 370 of 440 bowel segments (84%) in the non-glucagon group ( p=n.s.) Colonic distention at CT colonography is improved by dual positioning but not by the administration of intravenous glucagon. While our results suggest that other smooth muscle relaxants, including butyl scopolamine, may only have a limited role in improving colonic distention in CT colonography, further studies are required.

Treatment issues in type 2 diabetes.

This is the fifth in a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia, PA, in June 2001. It covers topics related to the treatment of type 2 diabetes. Alan Cherrington, Nashville, TN, examined the effect of insulin to inhibit hepatic glucose production. Using a dog preparation with somatostatin to block insulin and glucagon production and administration of insulin and glucagon into the portal vein, decreasing portal insulin to levels similar to those in the arterial circulation immediately increased hepatic glucose production via glycogenolysis, which was sustained over a period of several hours, with consequent hyperglycemia. There is a steep inverse dose-response curve of hepatic glucose production versus hepatic sinusoidal insulin levels. Tripling insulin quickly turns off hepatic glucose production. Glucose utilization by the liver in response to increasing insulin levels has a longer time course, taking several hours to reach maximal levels. This response is much less sensitive to changes in insulin levels than hepatic glucose production, and normal basal hepatic glucose utilization is very low. Muscle is less sensitive on a molar basis than in the liver, so that a tripling of insulin levels causes only a 50% increase in glucose utilization, compared with the more than sixfold increase in glucose uptake under maximal stimulation. Comparing the effects of first-phase and second-phase insulin release in response to glucagon, the former more potently inhibits glucose production. Insulin levels show similar first- and second-phase responses to a hyperglycemic clamp, and elimination of the first-phase insulin response leads to much greater hepatic glucose production, although it has little effect on glucose utilization. A recent study with nateglinide similarly showed a rapid insulin response and marked lessening of postprandial hyperglycemia (1). When intraduodenal glucose is given with dogs having somatostatin and portal catheters, a first-phase …

Radiological treatment of retained bile duct stones following recent surgery using glucagons

Retained common bile duct (CBD) stones pose an occasional problem following ductal exploration, in spite of completion cholangiography or choledochoscopy. We present a method for treating retained stones in the Radiology Department by biliary lavage via a transcystic tube (TCT) or a T-tube, after intravenous administration of glucagon. A TCT or T-tube is inserted following CBD exploration for multiple intrahepatic stones or when stones are fragmented to facilitate removal or flushing into the duodenum. A tube cholangiogram is performed on the 1st postoperative day. If any retained stones are encountered, 1 mg glucagon is administered intravenously and saline irrigation through the tube is done under fluoroscopic control, allowing the stone to pass to the duodenum. The cholangiogram is repeated 10-14 days later, before removing the tube. In case 1, transcystic CBD exploration was performed. Two stones were crushed and flushed into the duodenum. TCT cholangiography the following day. showed a 5-6-mm fragment causing complete obstruction. Following the use of glucagon and irrigation, the stone was observed passing into the duodenum, causing a brief mild episode of pain. In case 2, laparoscopic choledochotomy was performed to remove seven large stones. Completion choledochoscopy was satisfactory. T-tube cholangiography identified a small stone in the CBD, which was cleared with the help of glucagon. The current standard treatment for retained stones is endoscopic sphincterotomy. This is associated with morbidity, mortality, and significant additional cost. This new technique is a simple and safe alternative for retained CBD stones, most of which as small stones or fragments. Because glucagon causes intense relaxation of the sphincter of Oddi, the procedure should not take much longer than a routine tube cholangiogram. The safety of glucagon makes it possible to repeat the procedure if necessary.

Response of enzyme activities and metabolic intermediate concentrations to epinephrine administration in hepatopancreas and muscle of carp

SUMMARY: An experiment was carried out to investigate the effect of an intraperitoneal glucagon administration (60 μg/kg) on enzyme activities and metabolic intermediate concentrations in the hepatopancreas and muscle of common carp Cyprinus carpio. In the hepatopancreas, glycogen phosphorylase a activity together with cyclic adenosine-5′-monophosphate (AMP) concentration were significantly increased, and glycogen content was significantly decreased, at 1 h after the glucagon administration. Additionally, glucose-6-phosphatase and fructose-1,6-bisphosphatase activities as well as plasma glucose and free amino acid concentrations were increased after its administration. In the muscle, glucose and glycogen contents increased after the administration. Furthermore, the hormone administration also increased phosphofructokinase activity together with fructose-6-phosphate, AMP, and adenosine-5′-diphosphate concentrations and decreased adenosine-5′-triphosphate concentration. From 3 h after the administration, many parameter concentrations in both tissues showed a tendency to recover to the initial levels. These results suggest that glucagon administration enhanced glycogenolysis and gluconeogenesis in the hepatopancreas, and as a consequence, glucose was released into the bloodstream. The blood glucose seems to be metabolized through enhanced glycolysis and glycogenesis in the muscle.

Response of enzyme activities and metabolic intermediate concentrations to glucagon administration in hepatopancreas and muscle of carp +

Response of enzyme activities and metabolic intermediate concentrations to glucagon administration in hepatopancreas and muscle of carp +

Glucagon administration – underevaluated and undertaught

AbstractGlucagon treatment requires a manually dexterous ‘operator’ who is composed, confident and competent in the whole procedure. Anecdotal reports from parents of teenagers describing difficulties in administering this procedure during severe hypoglycaemia led us to investigate the ‘techniques’ of 136 parents (106 parents of teenagers and 30 parents of young children). A simulated administration by parents using Novo Nordisk Glucagen® Hypokits was timed, rated and compared with a group of diabetes health professionals. Parent's ‘real life’ experiences of education and administration were obtained with a standard questionnaire. Glucagon residues in syringes and vials were estimated in a laboratory. Sixty nine per cent had handling difficulties ranging from opening the container to drawing the correct dose into the syringe. There was no statistical difference in time taken to complete the procedure between the two parent groups. However there was a significant difference between parents and the professional group. Parents were not accurate in administering dosages as recommended. Young children weighing more than 25 kg would have received less than the required dose. All parents reported verbal instruction with demonstration of the procedure at initial education. We suggest that glucagon administration needs to be taught ‘hands on’ and the skill reassessed on an annual basis. Copyright © 2001 John Wiley &amp; Sons, Ltd.

Proximal stomach function in systemic sclerosis: relationship with autonomic nerve function.

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs 47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant-associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc.

Pancreatic and hepatic glycogen content in normoglycemic and hyperglycemic rats.

As judged from morphological criteria, glycogen accumulates to a larger extent in insulin-producing B-cells than in acinar cells of the pancreas in situations of sustained hyperglycemia. In the present study, the glycogen content of the pancreatic gland and liver was measured in either euglycemic or glucose-infused hyperglycemic control rats, as well as in streptozotocin-induced diabetic rats. Whilst the glycogen content of the pancreas was significantly higher in STZ rats than in control euglycemic rats, it was further enhanced in glucose-infused control rats, despite the fact that the latter animals were not more severely hyperglycemic and for a shorter time than STZ rats. From these measurements, it was estimated that, relative to wet weight, the glycogen content was, under the present experimental conditions, about 75 times higher in insulin-producing than other pancreatic cells. Moreover, it is proposed that the intravenous administration of glucagon may help in distinguishing between the glycogen present in the endocrine and exocrine moieties of the pancreatic gland, this hormone being apparently unable to provoke glycogenolysis in the exocrine pancreas, at variance with the situation prevailing in isolated pancreatic islets.

Interaction between glucagon and human corticotropin-releasing hormone or vasopressin on ACTH and cortisol secretion in humans

It is known that glucagon administration elicits ACTH and cortisol responses in humans, although this effect takes place after intramuscular or subcutaneous but not after the intravenous route of administration. The mechanisms underlying this stimulatory effect on corticotroph secretion are unknown but they are unrelated to glucose variations and stress-mediated actions. To throw further light on the stimulatory effect of i.m. glucagon on the pituitary-adrenal axis, using six normal young female volunteers (26-32 years, body mass index 19.7-22.5 kg/m(2)) we studied the interaction between glucagon (GLU; 0.017 mg/kg i.m.) and human corticotropin-releasing hormone (hCRH; 2.0 microg/kg i.v.) or vasopressin (AVP; 0.17 U/kg i.m.). The interactions between hCRH and AVP on the hypothalamo-pituitary-adrenal (HPA) axis and the GH response to GLU alone or combined with hCRH or AVP were also studied. GLU i.m. administration elicited a clear increase in ACTH (peak vs baseline, means+/-s.e.m.: 11.6+/-3.3 vs 4.2+/-0.3 pmol/l, P<0.05), cortisol (613.5+/-65.6 vs 436.9+/-19.3 nmol/l, P<0.05) and GH levels (11.6+/-3.4 vs 3.3+/-0.7 microg/l, P<0.05). The ACTH response to GLU (area under the curve: 426.4+/-80.9 pmol/l per 120 min) was higher than that to AVP (206.3+/-38.8 pmol/l per 120 min, P<0.02) and that to hCRH (299.8+/-39.8 pmol/l per 120 min) although this latter difference did not attain statistical significance. The GLU-induced cortisol response (28336.9+/-2430.7 nmol/l per 120 min) was similar to those after hCRH (24099.2+/-2075.2 nmol/l per 120 min) and AVP (21808.7+/-1948.2 nmol/l per 120 min). GLU and hCRH had an additive effect on ACTH (964.9+/-106.6 pmol/l per 120 min, P<0.02) and a less than additive effect on cortisol levels (35542.5+/-2720. 2 nmol/l per 120 min). Similarly, GLU and AVP had an additive effect on ACTH (825.6+/-139.6 pmol/l per 120 min, P<0.02) and an effect less than additive on cortisol levels (33059.2+/-1965.3 nmol/l per 120 min). The effects of GLU co-administered with hCRH or AVP were similar to those of the combined administration of hCRH and AVP on ACTH (906. 0+/-152.7 pmol/l per 120 min) and cortisol (34383.5+/-1669.2 nmol/l per 120min) levels. The GH response to GLU was not modified by hCRH or AVP. These results show that i.m. glucagon administration is a provocative stimulus of ACTH and cortisol secretion, at least as potent as hCRH and AVP. The ACTH-releasing effect of i.m. glucagon is not mediated by selective CRH or AVP stimulation but the possibility that both neurohormones play a role could be hypothesized.

3355 Troponin i determination to detect subclinical cardiac ischemia during ercp.

Introduction: Methodological/procedural risks of ERCP are well known, but cardiac risks have not been studied, specifically. Troponin I (TnI) is a cardio-selective enzyme that can aid in detection of even small amounts of myocardial damage. This prospective study examined the TnI levels of patients before and after ERCP to assess for cardiac injury, e.g. caused by administration of antimotility agents that can produce tachycardias (Scopolamine, Glucagon). Methods: 100 patients (57 f, 43 m, age 20-93, mean 62 y) were randomized prospectively to administration of Scopolamine or Glucagon as the antimotility agent during ERCP (30% diagnostic, 70% therapeutic). 65% of patients had one or more cardiovascular risk factors. TnI [normal value 0-0.4 ng/ml] was measured at baseline, at 8 h, and, if elevated, at 20 h post ERCP. Patients were sedated with Midazolam, Midazolam/Pentazocin or Propofol, given nasal O₂(2 l/min), and were monitored during ERCP for heart rate, blood pressure, pulse oximetry. Results: Mean duration of ERCP was 28 min. 8 patients (5 with Scopolamine, 3 with Glucagon) had elevated TnI levels: 6 already had elevated levels at baseline (0.5-2.5ng/ml; mean 1.13), with subsequent decrease to normal in 4 patients over the 8/20 h after ERCP. The remaining 4 (2 with TnI elevations at baseline, 2 with normal TnI at baseline) had a rise in TnI levels from 0-1.3 (mean 0.47) ng/ml at baseline to 0.9-18.4 (mean 5.48) ng/ml at 8 h, to 0.6-7.8 (mean 2.75) ng/ml at 20 h after ERCP. 3 of these 4 patients had ERCP's of more than 30 min in duration (range 32-115 min). In the patients with a rise in TnI no cardiac symptoms or complication occurred during or after the ERCP. There was no correlation of an increase in TnI with tachycardias (pulse >120), hypoxic episodes (O₂- Sat < 95%), or systolic BP elevations (>160 mm Hg). No difference was found between administration of Scopolamin versus Glucagon: Heartrates of >100/min and/or systolic BP >160 mm Hg occurred in 33 patients after Scopolamin and 34 patients after Glucagon without change in TnI. 22 patients had stable vital signs. Conclusions: In this study an increasing TnI level was observed in 4% of patients undergoing ERCP. This correlated only with duration of the procedure (>30 min). No difference was found with regard to choice of antimotility agent (Scopolamine versus Glucagon). No clinically relevant cardiac symptoms or cardiovascular problems resulted in any patient with TnI elevation. In this study ERCP appeared to be safe from a cardiovascular standpoint, even for multimorbid patients.

Release of osmolytes induced by phagocytosis and hormones in rat liver.

Betaine, taurine, and inositol participate as osmolytes in liver cell volume homeostasis and interfere with cell function. In this study we investigated whether osmolytes are also released from the intact liver independent of osmolarity changes. In the perfused rat liver, phagocytosis of carbon particles led to a four- to fivefold stimulation of taurine efflux into the effluent perfusate above basal release rates. This taurine release was inhibited by 70-80% by the anion exchange inhibitor DIDS or by pretreatment of the rats with gadolinium chloride. Administration of vasopressin, cAMP, extracellular ATP, and glucagon also increased release of betaine and/or taurine, whereas insulin, extracellular UTP, and adenosine were without effect. In isolated liver cells, it was shown that parenchymal cells and sinusoidal endothelial cells, but not Kupffer cells and hepatic stellate cells, release osmolytes upon hormone stimulation. This may be caused by a lack of hormone receptor expression in these cells, because single-cell fluorescence measurements revealed an increase of intracellular calcium concentration in response to vasopressin and glucagon in parenchymal cells and sinusoidal endothelial cells but not in Kupffer cells and hepatic stellate cells. The data show that Kupffer cells release osmolytes during phagocytosis via DIDS-sensitive anion channels. This mechanism may be used to compensate for the increase in cell volume induced by the ingestion of phagocytosable material. The physiological significance of hormone-induced osmolyte release remains to be evaluated.

A new caw of hepatic glycogen snthase deficiency. biochemical findings and comparison with reported cases

Hepatic glycogen synthase deficiency (GSD-0) is an autosomal recessive disorder first described in 1963. Fifteen cases in seven different families have been reported. Mutations in GYS2, the gene coding for liver glycogen synthase, were found in the four families studied. We report a new case of GSD-0 in a female patient born to healthy non-consanguineous French Canadian parents. She was referred for a family-history of hyperlipidemia at 7 years of age. In addition to increased plasma total cholesterol and triglyceride levels, workup revealed fasting hypoglycemia and ketonuria. Her only complaint was morning headaches. Growth and development were normal Physical exam including neurological exam was normal. Cerebral MRI and EEC were normal Biochemical findings consistent with the diagnosis included fasting hypoglycemia, ketonemia and hypoalaninemia, and postprandial hyperlactatemia and elevated plasma branched chain amino acid levels. Liver biopsy confirmed reduced glycogcn synthase activity. Ratio of active to inactive form of glycogen synthase was normal, suggesting reduced enzyme synthesis rather than synthesis of an inactive protein. Low hepatic glycogen content and mild to moderate liver stealosis were present. Plasma free carnitine concentrations decreased during fasting while esterified carnitine levels remained unchanged. In contrast to other cases, we twice observed an increase in blood glucose levels after administration of glucagon following 15 and 18 hours of fasting respectively (from 2.2 to 3.4 and 2.7 to 4.0 mmol/L respectively) Since her hepatic glycogen content was reduced, this might come from gluconcogenesis At 13 years of age, our patient still has fasting hypoglycemia although to a lesser degree. Her growth and intellectual development remain normal From our patient's clinical course and a review of the literature, we draw the following conclusions (1) non specific symptoms after overnight fasting were the presenting complaint in 6/16, 3 cases were brought to medical attention because of incidental findings, family history led to the diagnosis in 7 cases. (2) fasting hypoglycemia (16/16) and reduced liver glycogen content (8/8) are constant features, (3) other frequent biochemical findings include hyperlactatemia with feeding (13/16) and fasting hyperketonemia (9/16) and hypoalaninemia (8/16); (4) glucagon response after feeding is usually absent (4/6) but can be observed (2/6); (5) liver steatosis was observed in 5/8 cases. (6) growth and development are usually normal (12/16 and 13/16 respectively).

Evaluation of colonic diverticular disease in autosomal dominant polycystic kidney disease without end-stage renal disease.

A previous study had shown an increased prevalence (83%) of diverticula among patients with autosomal dominant polycystic kidney disease (ADPKD) with end-stage renal disease (ESRD) compared with other ESRD patients without ADPKD (32%). Others have also suggested an increased risk for diverticular complications in renal transplant recipients with ADPKD. To determine whether there was an increased occurrence of diverticula among non-ESRD patients with ADPKD, we studied 55 patients with ADPKD who were not receiving renal replacement therapy compared with 12 unaffected family members (non-ADPKD) and 59 random patients who had undergone barium enemas (control [C]). No study patient had a history of diverticular disease. All patients underwent a double-contrast barium enema after administration of glucagon. The occurrence, number, location, and size of diverticula were noted. There was no significant difference among the three groups in regard to sex (men: ADPKD, 42% versus non-ADPKD, 42% versus C, 37%) or age (ADPKD, 49.3 +/- 0.7 versus non-ADPKD, 51.2 +/- 2.1 versus C, 49 +/- 1 years). There was no significant difference in the percentage of patients with diverticula (ADPKD, 47% versus non-ADPKD, 58% versus C, 59%), the percentage with only right-colon diverticula (ADPKD, 5% versus non-ADPKD, 17% versus C, 5%), the mean number of diverticula in patients with diverticulosis (ADPKD, 13.8 versus non-ADPKD, 7.9 versus C, 9.9 diverticula), or the size of the largest diverticula (ADPKD, 9.5 versus non-ADPKD, 10.4 versus C, 10.5 mm). There was no significant difference in these variables between the patients with ADPKD with a creatinine clearance greater than 70 mL/min/1.73 m(2) (n = 25) or less than 70 mL/min/1.73 m(2). This study does not show the greater prevalence of diverticular disease in non-ESRD patients with ADPKD compared with the general population. Thus, patients with ADPKD need not be considered at greater risk for diverticular disease than the general population.

Disruption of filamentous actin diminishes hormonally evoked Ca 2+ responses in rat liver

Previous studies have suggested a role for the actin cytoskeleton in hormonally evoked Ca 2+ signaling in the liver. Here, we present evidence supporting a connection between filamentous actin (F-actin) organization and the ability of vasopressin and glucagon to increase cytosolic free-Ca 2+ ([Ca 2+] i) levels. F-actin was disrupted in hepatic cells by perfusion of rat liver with cytochalasin D. Epifluorescence microscopy of subsequently isolated cells showed reduced cortical fluorescent phalloidin staining in cytochalasin D-treated liver cells. Cytochalasin D pretreatment of liver cells reduced the vasopressin-stimulated elevation of [Ca 2+] i by 60% and of glucagon by 50%. Experiments performed on cytochalasin D-treated cells using Mn 2+ as an indicator of Ca 2+ influx quenched fura-2 fluorescence signals following vasopressin administration. This indicates that a structurally intact cortical F-actin web is not a prerequisite for the influx of calcium. Therefore, the attenuation of the increase in cytosolic calcium observed in cytochalasin D-treated liver cells was likely caused either by the depletion of the calcium store by treatment with cytochalasin D or by the need for an intact cytoskeletal structure for its release. Because the resting level of calcium did not change in cells exposed to cytochalasin D, the latter is likely. The reduced [Ca 2+] i response may be the mechanism by which cytochalasin D pretreatment inhibits vasopressin-induced metabolic effects. Cytochalasin D pretreatment also decreased the ability of glucagon to stimulate gluconeogenesis and reduced the stimulation of O 2 uptake usually observed following glucagon administration. In conclusion, these results suggest that the hormonal elevation of [Ca 2+] i and resultant activation of specific metabolic pathways require normal F-actin organization.