Intravenous Administration Of Glucagon Research Articles

1301-P: Glucagon Stimulation Test—Is It Time for an Easy Interpretation Proposal?

Background and Aims. Guidelines suggest the use of c-peptide in case of ambiguous diabetes. Glucagon stimulation test (GST), with the intravenous administration of glucagon 1 mg, is a 10-minutes test and it is suitable in clinical practice. It can describe residual beta-cell function although an easy way to identify from this test the type of diabetes or need for insulin in the short term is not available. The aims of this pilot study were to describe c-peptide response during GST and to identify classes of subjects corresponding to different types of diabetes or need of insulin. Methods: We retrospectively recorded c-peptide levels of adults with ambiguous diabetes who underwent to GST. We divided subjects in 4 classes according to basal c-peptide (BCP) and to mean stimulated c-peptide increase (SCPi): class 1 (BCP <0.5 and SCPi <0.7 mmol/L from basal levels); class 2 (BCP <0.5 mmol/L and SCPi ≥0.7 mmol/L), class 3 (BCP ≥0.5 mmol/L and SCPi <0.7 mmol/L); class 4 (BCP ≥0.5 mmol/L and SCPi ≥0.7 mmol/L). Data about antibody positivity for anti-GAD and I.C.A. (Ab+) and need for insulin within two months were recorded. Results: We enrolled 61 subjects, age 48.4 (14.6) years [mean (standard deviation)]. 7 subjects (11%) were included in class 1. Mean basal c-peptide was 0.3 mmol/L. 5 subjects (71%) were Ab+ and all required insulin. None of the participants were included in class 2. 18 subjects (29.5%) were included in class 3. Mean basal c-peptide was 1.0 mmo/L. 11 (61%) of class 3 subjects were Ab+ and required insulin within 2 months. 36 subjects (59.5%) were included in class 4. Mean basal c-peptide was 1.8 mmol/L. 5 (13%) of them required insulin therapy within 2 months and 4 (11%) were Ab+. Class 1 and 3 presented with lower BMI than class 4 (p<0.001). Conclusions: In those preliminary data subjects in class 1 are more likely type 1 diabetes, while subjects in class 3 are more likely T1DM or LADA requiring insulin in the short term. Those preliminary data suggest an easy interpretation for GST to include it more frequently in clinical practice. Disclosure A.Rizzi: None. L.Tartaglione: None. S.Gugliandolo: None. E.Di stasio: None. A.Barberio: None. D.Pitocco: None.

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.

Intraperitoneal, subcutaneous and intravenous glucagon delivery and subsequent glucose response in rats: a randomized controlled crossover trial

ObjectiveHypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon...

Glucagon facilitates colonoscopy and reduces patient discomfort

Randomized placebo-controlled trials on the effectiveness of glucagon in colonoscopy were conducted more than a decade ago and the outcomes varied for each study. Since then, techniques and imaging technology in colonoscopy have steadily improved. The aim of this study was to re-evaluate the effectiveness of glucagon as an antispasmodic, which may facilitate smooth scope intubation and reduce patient discomfort during screening colonoscopy under current equipment settings. A total of 70 patients undergoing colonoscopy under conscious sedation were randomized into two groups: a group with intravenous administration of 1 mg glucagon and a placebo group. After colonoscopy, patients completed questionnaires on pain, abdominal fullness, and acceptance of future colonoscopy. Difficulty in scope manipulation was scored by endoscopists, and times for cecal intubation, observation, and the number of polyps detected by colonoscopy were also recorded. In addition, we evaluated patient discomfort objectively with a newly developed portable analyzer of salivary amylase activity. This study was performed double-blind, and assignments were not disclosed to patients or to endoscopists. Scores for acceptance for future colonoscopy, pain, abdominal fullness, and scope manipulation were significantly lower in the glucagon group. Salivary amylase activity, determined at the time the scope was inserted to the cecum, was significantly lower in the glucagon group, and cecal intubation time was significantly shorter in the glucagon group. Observation time and polyp detection rate were not significantly different between the groups. These results indicate that intravenous administration of glucagon can reduce patient discomfort and improve scope intubation during screening colonoscopy.

Glucagon-Induced Vasospasm of Hepatic Artery Branches During Visceral Angiography

Glucagon is often used in radiology to decrease bowel motility for enhanced imaging, including visceral digital subtraction angiography. We present a case in which branch hepatic artery vasospasm followed the intravenous administration of glucagon during visceral angiography.

Noninvasive assessment of the effects of glucagon on the gastric slow wave

Hyperglycemic effects on the gastric slow wave are not well understood, and no studies have examined the effects that hyperglycemia has on gastric slow wave magnetic fields. We recorded multichannel magnetogastrograms (MGGs) before and after intravenous administration of glucagon and subsequent modest hyperglycemia in 20 normal volunteers. Normal slow waves were evident in baseline MGG recordings from all 20 subjects, but within 15 min after glucagon had been given, we noted significant effects on MGG signals. In addition to an overall decrease in the slow wave frequency from 2.9 +/- 0.5 cycles per min (cpm) to 2.2 +/- 0.1 cpm (P < 0.05), we observed significant changes in the number and range of spectral peaks recorded. Furthermore, the propagation velocity determined from surface current density maps computed from the multichannel MGG decreased significantly (7.1 +/- 0.8 mm/s to 5.0 +/- 0.3 mm/s, P < 0.05). This is the first study of biomagnetic effects of hyperglycemia in normal subjects. Our results suggest that the analysis of the MGG provides parameter quantification for gastric electrical activity specific to and characteristic of slow wave abnormalities associated with increased serum glucose by injection of glucagon.

Glucagon receptor expression and glucagon stimulation of ghrelin secretion in rat stomach

The present study was performed to evaluate the role of glucagon in the regulation of ghrelin secretion from the rat stomach. mRNA for ghrelin and glucagon receptor was expressed predominantly in the lower body and pylorus of stomach, but little or not in the upper body and cardia. Ghrelin- and glucagon receptor-immunoreactive cells were detected in lamina propria mucosae of stomach and some cells expressed both. Intravenous administration of glucagon caused transient increases in both acyl- and desacyl-ghrelin levels in the gastric vein within 10 min, which was followed by gradual increases in desacyl-ghrelin levels until 60 min. Steady state levels of ghrelin mRNA in the stomach were increased by 1.9-fold 20 min after glucagon administration, but not at 5 or 120 min. These results suggest that glucagon stimulates acute release of both forms of ghrelin and thereafter upregulates synthesis and release of desacyl-ghrelin in the rat stomach.

Does intravenous glucagon improve common bile duct visualisation during magnetic resonance cholangiopancreatography? Results in 42 patients

Introduction: Magnetic resonance cholangiopancreatography (MRCP) has been demonstrated as a reliable, non-invasive means of biliary tract imaging among patients with suspected choledocholithiasis. The aim of this study was to establish the impact of intravenous glucagon administration (IVGA) upon visualisation of the common bile duct (CBD) and ampulla of Vater during MRCP. Materials and methods: Forty-two consecutive, non-diabetic subjects with a working diagnosis of symptomatic choledocholithiasis were scanned, pre- and post-IVGA using the half-Fourier, single shot, turbo-spin-echo (HASTE) sequence. Maximum intensity projections (optimised for the extra-hepatic biliary tree and ampulla of Vater) were reviewed blindly by three consultant radiologists. The CBD images were graded (0–3) according to the length of duct seen. The ampullary images were graded according to whether to it was visualised clearly (1), or not (0). Results: Following IVGA the CBD was visualised at grade 3 (75–100% of length seen) in 14 additional patients compared with images prior to IVGA. Furthermore, ampullary visualisation was considered diagnostic in 18 additional patients post-IVGA. No glucagon-associated adverse effects were observed. Conclusion: These results demonstrate that IVGA improved visualisation of the CBD and ampulla of Vater during magnetic resonance cholangiopanctreatography. This may reduce the requirement for repeat investigation or recourse to invasive diagnostic procedures (e.g. endoscopic retrograde cholangiopancreatography (ERCP)).

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.

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.

A Review of Potential Cardiovascular Uses of Intravenous Glucagon Administration

Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocker overdose and has evidence for use in verapamil and imipramine overdose as well. Glucagon has been used as adjunctive therapy in shock situations and heart failure but is inferior to catecholamines. An interesting potential indication for glucagon is in treating postcountershock asystole.

The utility of intracorporeal ultrasonography for screening of the bile duct during laparoscopic cholecystectomy

Different strategies and imaging modalities have been used to detect common bile duct (CBD) stones during laparoscopic cholecystectomy. We prospectively compared fluoroscopic intraoperative cholangiography (FIOC) and laparoscopic intracorporeal ultrasonography (LICU) in patients undergoing laparoscopic cholecystectomy for this purpose. In a consecutive series of 607 laparoscopic cholecystectomies, FIOC was used in the first 407 patients, whereas LICU was preferentially applied to the subsequent 200 patients. When LICU documented CBD stones, the duct was flushed with saline solution after intravenous administration of glucagon, and stone persistence or absence was confirmed by FIOC and/or repeat LICU. In the FIOC group, 10 patients were converted to open cholecystectomy and 16 patients did not undergo FIOC. Among the remaining 381 patients, FIOC was successful in 370 (97%). In the LICU group, two patients were converted and LICU was not performed in 26 patients. In the remaining 172 patients, the cystic duct (CBD) junction and the CBD were visualized in all cases ( P<0.05 vs. FIOC). The mean (± SEM) times required to complete FIOC and LICU were 15.1 ± 0.4 minutes and 5.3 ± 0.2 minutes, respectively ( P <0.0001). Choledocholithiasis was detected in 25 patients (7%) undergoing FIOC and in 22 patients (13%) undergoing LICU ( P <0.05). In the LICU group, the mean sizes of the stones cleared by ampullary dilatation and flushing (17 of 22, 77%) and those requiring more invasive methods (5 of 22, 23%) were 1.6 ± 0.2 mm and 2.7 ± 0.3 mm, respectively ( P <0.01). Sludge was seen in the CBD by LICU in 10 patients (6%), which disappeared with flushing in all cases. LICU is accurate, safe, and permits more rapid evaluation of bile duct stones than FIOC during laparoscopic cholecystectomy. LICU may be overly sensitive in detecting small stones and sludge, which are of questionable significance. Stones 2 mm or less can usually be cleared by flushing, whereas larger ones often require invasive techniques for removal.

Hydro-CT in patients with gastric cancer: preoperative radiologic staging.

A total of 35 patients (age range 35-78 years) with gastric tumors on the lesser curve, or in the antro-pyloric region, underwent angio-CT in the prone position after filling the stomach with 500 ml of water and intravenous administration of glucagon. The films were reviewed by three radiologists independently, staging each tumor according to the TNM classification preoperatively. The overall accuracy of tumor staging ranged between 66-77 %, overstaging between 17-25 %, and understaging between 3-8.5 %. The diagnostic sensitivity, specificity, and accuracy for serosal invasion ranged between 90 and 100, 76 and 84, and 80-88 %, respectively, and the overall accuracy for N staging was 46, 48, and 51 % for the three observers. If, however, N1 and N2 tumors were considered as a single group, N-stage accuracy increased, ranging between 63 and 77 %. The "K test" for analyzing the interobserver agreement was 60 %, i. e., the diagnostic results are reproducible. Water filling of the stomach optimizes visualization of the gastric wall on contrast-enhanced CT. The prone position and drug-induced hypotony allows for good distension without any disturbing artifact reduction obscuring the lower gastric body.

Hepatic contrast enhancement at CT: influence of intravenous glucagon in a canine model.

To investigate the effect of glucagon on the timing and degree of hepatic enhancement at computed tomography. Each of 11 dogs underwent injection of contrast material at two uniphasic rates (0.5 mL/sec and 1.5 mL/sec) with without previous intravenous administration of 0.5 mg of glucagon. Scans were obtained at a single intrahepatic level every 3.5 seconds for 120-160 seconds. Attenuation values in the liver, aorta, portal vein, and inferior vena cava (IVC) were measured. Glucagon administration was associated with greater hepatic enhancement throughout the study: Peak hepatic enhancement was greater at contrast injection rates of 0.5 mL/sec (P = .021) and 1.5 mL/sec (P = .0001). Peak hepatic enhancement also occurred earlier during the glucagon runs. Portal vein enhancement was greater during the glucagon runs at an injection rate of 1.5 mL/sec (P = .032). IVC enhancement was greater during the nonglucagon runs at 0.5 mL/sec (P = .013) and at 1.5 mL/sec (P = .005). Intravenous administration of glucagon before contrast material injection produces greater and more rapid hepatic enhancement in a canine model.

Does routine intravenous glucagon administration facilitate colonoscopy? A randomized trial

Background: Previous studies on the routine use of glucagon in colonoscopy have produced conflicting results.Methods: Two separate studies were performed. In one study (Study 1), 80 consecutive patients were randomized after cecal intubation to receive 1 mg glucagon ( n = 41) or placebo ( n = 39), intravenously, in double-blind fashion. In a second study (Study 2) 90 sedated patients undergoing colonoscopy were randomized to receive 1 mg glucagon ( n = 46) or placebo ( n = 44), intravenously, just before colonoscope insertion. In each study, colonoscope insertion and withdrawal time, therapeutic intervention time, the presence and severity of colonic spasm, colonoscopy yield, and side effects were recorded.Results: Mean withdrawal time in Study 1 was similar in those receiving glucagon (6.85 min) and in those receiving placebo (6.92 min). Mean insertion time in Study 2 (5.07 min) was identical between groups. Spasm scores and colonoscopy yield did not differ between glucagon and placebo in either study. There was a trend toward more side effects (nausea and vomiting) with glucagon in Study 1. Glucagon did not facilitate insertion or withdrawal in the subset of patients with diverticulosis.Conclusions: Routine use of intravenous glucagon in a dosage of 1 mg does not facilitate colonoscopy by experienced examiners. (Gastrointest Endosc 1995;42:346-50.)

Gastric tone determines the sensitivity of the stomach to distention

Background/Aims: Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. Methods: Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure levels (in 2-mm Hg increments) and at fixed volume levels (in 200-mL increments) were performed in 10 healthy subjects per group; perception was measured on a 0–6 scale. Distentions were performed during intravenous infusion of saline (basal) and during gastric relaxation by intravenous administration of glucagon (4.8-μg/kg bolus plus 9.6 μg · kg −1 · h −1 infusion). Results: The same distending pressures tested produced 30% ± 9% larger intragastric volumes and 80% ± 44% higher perception scores when the stomach was relaxed by glucagon ( P < 0.05 vs. basal for both). In contrast, the same distending volumes tested produced 25% ± 7% lower intragastric pressures and 21% ± 12% lower perception scores when the stomach was relaxed ( P < 0.05 vs. basal for both). Conclusions: Epigastric symptoms in response to gastric distention are influenced by both the intragastric pressure and the intragastric volume.

Suppression of gluconeogenesis after a 3-day fast does not deplete liver glycogen in patients with NIDDM.

To determine the effect of inhibition of gluconeogenesis on liver glycogen stores in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3-[3H]glucose) and [U-14C]alanine incorporation into glucose (alanine gluconeogenesis [Ala-GNG]) were determined before and during EtOH administration, and residual glycogen stores were assessed by the incremental glucose response to glucagon (glucoseAUC). Hepatic glucose output (HGO) was closely correlated with plasma glucose levels (r = 0.71, P < 0.001) after the 3-day fast and was significantly greater in the diabetic compared with the nondiabetic subjects (13.8 +/- 1.4 vs. 7.6 +/- 0.6 mumol.kg-1 FFM.min-1, P < 0.01). During the 120-min EtOH infusion, Ala-GNG fell by more than 50% in both groups and did not increase after intravenous glucagon administration. HGO fell modestly in both the diabetic and nondiabetic subjects during the first 30 min of EtOH infusion and stabilized thereafter. In contrast to Ala-GNG, HGO increased significantly after intravenous glucagon administration in both the diabetic and nondiabetic subjects, but the increase was significantly greater in the patients with NIDDM (P < 0.01). The glucose area under the curve in response to glucagon (glucoseAUC) was lower in the presence of EtOH than in its absence (14.9 +/- 7 vs. 68 +/- 15.6 mM/min, P < 0.01) in the obese nondiabetic subjects, which suggests a decrease in liver glycogen stores.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Concentrations of Islet Amyloid Polypeptide After Glucagon Administration in Type 2 Diabetic Patients and Non‐diabetic Subjects

Islet amyloid polypeptide (IAPP) is the main constituent of pancreatic islet amyloid, observed in the pancreases from patients with Type 2 diabetes mellitus. IAPP is synthesized by the pancreatic beta-cells. In order to study the secretion characteristics of IAPP in Type 2 diabetes mellitus, plasma IAPP was measured during a provocation test with glucagon in 33 Type 2 diabetic patients and 18 non-diabetic subjects. The median fasting IAPP level was 5.7 (range 1.1-13.1) pmol l-1 in the 27 patients treated with oral hypoglycaemic agents and 2.7 (1.9-5.9) in the 6 patients on insulin. In the non-diabetic group fasting IAPP was 5.7 (2.2-10.1). Six minutes after glucagon administration median IAPP rose to 9.4 (1.7-31.0) and 6.1 (5.1-10.2) in the respective diabetic groups, and to 16.8 (4.0-41.0) in the non-diabetic subjects (p << 0.05). The correlation coefficient between change in IAPP and change in C-peptide was 0.68 in the diabetic group. We conclude that intravenous administration of glucagon stimulates IAPP release from the beta-cell. This provocation test is easy to perform and can be used on a large scale in the study of IAPP secretion in Type 2 diabetes mellitus.

The relation between clinical manifestations of polycystic ovary syndrome and β‐cell function

Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome. Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria. Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG. There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients. The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Pancreatic B-cell functioning after intravenous glucagon administration in anorexia nervosa.

Abnormal glucose tolerance is often found in patients with anorexia nervosa (AN). We attempted to evaluate pancreatic B-cell functioning after intravenous glucagon administration. Fourteen patients with the restricting type of AN (percentage of ideal body weight 71.5 +/- 1.6%, mean +/- SE) and 6 patients with the bulimic type of AN (77.0 +/- 3.0%) were studied. After an overnight fast, glucagon (0.02 mg/kg) was injected i.v. into all subjects and 6 normal controls. Blood samples were obtained at 0, 5, 30, 60, 90 and 120 min to measure blood glucose (BS), serum insulin (IRI) and C-peptide (CPR). The same tests were repeated in 8 patients with restricting AN after therapy and restoration of body weight (85.9 +/- 1.0% of ideal body weight). BS responses did not differ among the groups. Peak serum levels (5 min) of both IRI and CPR in restricting AN patients were significantly lower than those in bulimic AN patients and in normal controls. BS, IRI and CPR concentrations did not change significantly following restoration of body weight. Pancreatic B-cell dysfunction after glucagon administration was observed in restricting AN patients and the abnormality persisted after short-term weight restoration.