Glucagon Injection Research Articles

Low-Order Nonlinear Animal Model of Glucose Dynamics for a Bihormonal Intraperitoneal Artificial Pancreas.

The design of an Artificial Pancreas (AP) to regulate blood glucose levels requires reliable control methods. Model Predictive Control has emerged as a promising approach for glycemia control. However, model-based control methods require computationally simple and identifiable mathematical models that represent glucose dynamics accurately, which is challenging due to the complexity of glucose homeostasis. In this work, a simple model is deduced to estimate blood glucose concentration in subjects with Type 1 Diabetes Mellitus (T1DM). Novel features in the model are power-law kinetics for intraperitoneal insulin absorption and a separate glucagon sensitivity state. Profile likelihood and a method based on singular value decomposition of the sensitivity matrix are carried out to assess parameter identifiability and guide a model reduction for improving the identification of parameters. A reduced model with 10 parameters is obtained and calibrated, showing good fit to experimental data from pigs where insulin and glucagon boluses were delivered in the intraperitoneal cavity. A simple model with power-law kinetics can accurately represent glucose dynamics submitted to intraperitoneal insulin and glucagon injections. The reduced model was found to exhibit local practical as well as structural identifiability. The proposed model facilitates intraperitoneal bi-hormonal model-based closed-loop control in animal trials.

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency.

Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks. The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients. This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test. The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Long-term normothermic machine preservation of human livers: what is needed to succeed?

Although short-term machine perfusion (≤24 h) allows for resuscitation and viability assessment of high-risk donor livers, the donor organ shortage might be further remedied by long-term perfusion machines. Extended preservation of injured donor livers may allow reconditioning, repairing, and regeneration. This review summarizes the necessary requirements and challenges for long-term liver machine preservation, which requires integrating multiple core physiological functions to mimic the physiological environment inside the body. A pump simulates the heart in the perfusion system, including automatically controlled adjustment of flow and pressure settings. Oxygenation and ventilation are required to account for the absence of the lungs combined with continuous blood gas analysis. To avoid pressure necrosis and achieve heterogenic tissue perfusion during preservation, diaphragm movement should be simulated. An artificial kidney is required to remove waste products and control the perfusion solution's composition. The perfusate requires an oxygen carrier, but will also be challenged by coagulation and activation of the immune system. The role of the pancreas can be mimicked through closed-loop control of glucose concentrations by automatic injection of insulin or glucagon. Nutrients and bile salts, generally transported from the intestine to the liver, have to be supplemented when preserving livers long term. Especially for long-term perfusion, the container should allow maintenance of sterility. In summary, the main challenge to develop a long-term perfusion machine is to maintain the liver's homeostasis in a sterile, carefully controlled environment. Long-term machine preservation of human livers may allow organ regeneration and repair, thereby ultimately solving the shortage of donor livers.

Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies

IntroductionTo prevent medical sequelae of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use, liquid stable glucagon, administered subcutaneously by glucagon autoinjector (GAI), Gvoke HypoPen (glucagon...

New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

Molecular identification of glucose transporter 4: The responsiveness to starvation, glucose, insulin and glucagon on glucose transporter 4 in common carp (Cyprinus carpio L.).

Glucose transporter 4 (GLUT4) is comprehensively investigated in mammals, while the comparative research of GLUT4 in common carp is deficient. To investigate the function of GLUT4, carp glut4 was first isolated. The open reading frame of carp glut4 was 1518 bp in length, encoding 505 amino acids. A high-sequence homology was identified in carp and teleost, and the phylogenetic tree displayed that the carp GLUT4 was clustered with the teleost. A high level of glut4 mRNA was analysed in fat, red muscle and white muscle. After fasting treatment, glut4 mRNA expression was increased significantly in muscle. In the oral glucose tolerance test experiment, glut4 mRNA was also significantly elevated in muscle, gut and fat. Furthermore, intraperitoneal injection of insulin resulted in the upregulation of glut4 gene expression significantly in white muscle, gut and fat. On the contrary, the glut4 mRNA level in the white muscle, gut and fat was markedly downregulated after glucagon injection. These results suggest that GLUT4 might play important roles in food intake and could be regulated by nutrient condition, insulin and glucagon in common carp. Our study is the first to report on GLUT4 in common carp. These data provide a basis for further study on fish GLUT4.

An Evaluation of Glucagon Injection Anxiety and Its Association with the Fear of Hypoglycemia among the Parents of Children with Type 1 Diabetes

Objective:Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration.Methods:Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA).Results:Sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child’s age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation±2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration.Conclusion:The results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents’ self-confidence including annual refresher training for home glucagon administration.

A Case of Autoimmune Hypoglycemia (Insulin Autoimmune Syndrome)

Introduction: Insulin Autoimmune Syndrome (IAS) is a condition caused by Insulin Autoantibody (IAA). IAS was initially reported in 1970 by Yukimasa Hirata from Japan. From 1970 to 2009, 380 cases were reported worldwide. We report a case of IAS in an African-American man who had recurrent episodes of syncope secondary to hypoglycemia. Case Report: A 50-year-old African American man with hypertension presented to emergency room after syncope. His initial blood glucose (BG) was 27 mg/dl. After Dextrose and glucagon injection, BG became 270 and he regained consciousness without any deficit. Vital signs and physical examination were unremarkable. He was not on any medication, and had no access to insulin or oral hypoglycemic agents. No family history of endocrine disorders, malignancy or autoimmune diseases were reported. He had been hospitalized two times for syncope secondary to hypoglycemia. During hospitalization, fasting insulin level was >1000 IU/ml with high C-peptide (3.5ng/ml). Hypoglycemic agents assay was negative. During outpatient follow-ups, fasting labs showed C-peptide 1.59 ng/ml, Insulin antibody 37.6 U/ml while venous BG was 65 mg/dl. Random BG at different occasions were 65, 68 and 55 mg/dl. HbA1C was normal. BMI was gradually increased from 32.4 to 34.8 in 6 months. During the third hospitalization, fasting venous BG were 45 and 57 on two different days, Insulin was 2111 IU/ml and C-Peptide was 1.78 ng/ml. Other labs including cortisol and TSH were normal. CT abdomen was unremarkable. Discussion: In IAS, Insulin secreted after meal is bound by IAA. It causes hyperglycemia unchecked which triggers further insulin secretion. When the bound insulin dissociates from antibodies, it causes significant hyperinsulinemia and subsequent hypoglycemia. IAS can occur regardless of previous insulin exposure, as a solitary autoimmune manifestation or in association with other autoimmune disorders. It can be induced by drugs that contain sulfhydryl group. Etiology of IAS is still not fully understood but there are theories that genetic predisposition such as class II Human Leukocyte Antigen (HLA) and environmental triggers such as medications, viruses, hematological diseases etc. might play a role. In our patient, failure to test IAA in past admissions and lack of continuity of care delayed the diagnosis. Conclusion: IAS should be considered especially in those who have no clear etiology of hypoglycemia in order to avoid unnecessary diagnostic and therapeutic procedures. Gold standard test for definitive diagnosis is IAA. As IAS is frequently self-remitting, supportive management is usually recommended. In severe cases, pharmacotherapies that reduce insulin secretion and immunosuppressants are occasionally necessary. But there is still no study that compares different treatment measures.

Inhaled Glucagon

Until now injectable glucagon was the only available treatment used in the management of severe hypoglycemia wherein glucagon had to be prepared in several steps before administration. This method of delivery of injectable glucagon being cumbersome and unappealing for a wide majority of the patients had led to a search for an alternative route of drug delivery. Intranasal (IN) glucagon now serves an efficient, safe, easy to administer, and a favorable substitute to glucagon injections. This ready-to-use device stands in clear contrast to overcome the limitations associated with the currently available glucagon preparations, which has emerged a key advancement in the management of severe hypoglycemia in adolescents and children with type 1 diabetes. IN glucagon is now being developed and studied in other countries as well to meet the unmet need for an easy and convenient glucagon administration. This review covers the basic information of nasal glucagon, trials on nasal glucagon in children's and adults, and its potential uses, limitations, and future scope in practice.

Nasal glucagon: A new hope for severe hypoglycemia in type 1 diabetes

Until now, injectable glucagon was the only available treatment used in the management of severe hypoglycemia wherein glucagon had to be prepared in several steps before administration. This method of delivery of injectable glucagon being cumbersome and unappealing for wide majority of the patients had led to a search for an alternative route of drug delivery. nasal glucagon (NG) now serves an efficient, safe, easy-to-administer, and a favorable substitute to glucagon injections. This ready to use device stand in clear contrast to overcome the limitations associated with the currently available glucagon preparations has emerged a key advancement in the management of severe hypoglycemia in adolescents and children with type 1 diabetes. NG is now being developed and studied in other countries as well to meet the unmet need for an easy and convenient glucagon administration. This review covers the basic information of nasal glucagon, trials on nasal glucagon in children and adults and its potential uses, limitations, and future scope in practice.

Dasiglucagon, a Ready-To-Use Glucagon Analog, For Rapid And Effective Treatment of Severe Hypoglycemia: a Phase 3, Randomized Controlled Trial in Children With Type 1 Diabetes

Background Dasiglucagon, a novel glucagon analog, is in development for the treatment of hypoglycemia. Objective: To assess the safety and efficacy of dasiglucagon via HypoPal® auto-injector as a rapid and dependable treatment for hypoglycemia in children with T1DM. Methods NCT03667053, a Phase 3, double-blind trial (N=42), randomized children (6-11 years: n=16; 12-17 years: n=26), 2:1:1 to a single subcutaneous injection of dasiglucagon (0.6 mg), placebo, or glucagon (GlucaGen®) following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery (first PG increase ≥ 20 mg/dL after treatment initiation). Results Median time (95% CI) to PG recovery was 10 min (8, 12) for dasiglucagon vs 30 min (20, –) for placebo (primary comparison, P < 0.001); and 10 min (8, 12) for GlucaGen®. Using linear interpolation, the median estimated true time to recovery was 8.7 min (6.9, 10.6) for dasiglucagon, 29.3 min (18.5, –) for placebo and 9.8 min (7.4, 10.6) for GlucaGen®. No safety concerns noted. Nausea and vomiting, known glucagon side effects, were reported for dasiglucagon (6-11 years: nausea [25%], vomiting [25%]; 12 17 years: nausea [92%], vomiting [67%]) and GlucaGen® (6-11 years: nausea [50%], vomiting [25%]; 12-17 years: nausea [17%], vomiting [0%]). No relationship was found between dasiglucagon exposure (AUC0 5h or Cmax) and nausea or vomiting. Conclusions In children with T1DM, dasiglucagon results in rapid and reliable correction of PG levels following induced hypoglycemia. The overall safety profile of dasiglucagon is similar to that of lyophilized glucagon, offering a convenient, rapid, and ready-to-use treatment for severe hypoglycemia.

Difficulties in Correction of Recurrent Hypoglycemia in a Patient With a Progressive Course of Malignant Metastatic Insulinoma

This article describes a clinical observation of a patient with a progressive course of malignant metastatic insulinoma, despite repeated embolization and chemoembolization (CE) of the right and left hepatic arteries with doxorubicin and gemcitabine, with metastatic liver lesion and subsequent increase in the size of secondary foci. The key clinical problem was severe recurrent hypoglycemia, which persisted against the background of massive intravenous (IV) glucose infusions, short-acting somatostatin therapy, and subcutaneous (SC) glucagon injections, which not only was an impediment to the pathogenic cytostatic therapy but also has led to the fatal outcome of the patient. J Endocrinol Metab. 2020;10(5):140-143 doi: https://doi.org/10.14740/jem666

Comparison of a combination test (1 μg ACTH test plus glucagon test) versus 1 μg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders.

To investigate whether a combination of the low-dose (1 μg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 μg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 μg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

1053-P: Dasiglucagon Hypopal Autoinjector as a Fast and Effective Treatment for Severe Hypoglycemia: Results of a Phase 3 Trial

Severe hypoglycemia is a major concern for patients with diabetes on insulin therapy. Rescue requires caregivers to provide effective treatment, including glucagon injections. Dasiglucagon is a stable glucagon analog in development to be administered with the HypoPal® auto-injector for treatment of severe hypoglycemia. This phase 3 trial, ZP4207-17145, assessed the clinical efficacy and safety of 0.6 mg dasiglucagon subcutaneous (SC) administered via the HypoPal® auto-injector compared with placebo. In total, 45 eligible patients with T1D were randomized (3:1) to dasiglucagon or placebo and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose. Dasiglucagon injection provided a fast and effective increase in PG. The median time (95% CI) to recovery based on sampling time was 10 (8.0, 12.0) min for dasiglucagon and 35 (20.0, -) min for placebo (p&amp;lt;0.0001). The median (95% CI) estimated true time to recovery (interpolated between sampling times) was 9.3 (7.8, 10.3) min for dasiglucagon and 25.8 (19.2, 34.8) min for placebo. Nausea and vomiting are well-known side effects of glucagon and were reported in 61.8% and 29.8% of patients receiving dasiglucagon, respectively. Nausea was reported in 10% of patients receiving placebo. No safety concerns were raised for dasiglucagon. In conclusion, dasiglucagon 0.6mg SC administered via the HypoPal® auto-injector provided fast and effective recovery from hypoglycemia. The results are consistent with previously reported results from a pivotal phase 3 trial testing dasiglucagon administered via a pre-filled syringe, NCT03378635, where a median time to recovery of 10 min was also observed. Disclosure T.S. Bailey: Consultant; Self; Abbott, LifeScan, Inc., Novo Nordisk A/S, Sanofi US. Research Support; Self; Abbott, Ascensia Diabetes Care, Capillary Biomedical, Inc., Dance Biopharm Holdings, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Medtronic, Medtrum, Novo Nordisk A/S, REMD Biotherapeutics, Sanofi-Aventis, Senseonics, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S. Speaker’s Bureau; Self; Medtronic, Sanofi US. J. Willard: None. L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. L.S. List: Employee; Spouse/Partner; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S, Zealand Pharma A/S. A.E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S.

Patient preparation and image quality in female pelvic MRI: recommendations revisited.

To assess whether with recent MR technology current patient preparation literature recommendations for female pelvic MRI are still valid and how they are influencing the position of the female pelvic organs, image quality, and diagnostic confidence. This prospective study was performed in two centres. The effects of bladder filling (empty, moderate, full; n = 26), fasting, saturation band (n = 25), and menstrual cycle (n = 25) were assessed in healthy subjects in centre 1, while the effect of intravenous glucagon application was evaluated in 20 patients with benign conditions in centre 2. Images of the pelvis were acquired using 1.5-T MRI with T2-weighted turbo spin echo imaging in sagittal and (angulated) transaxial planes. The analysis was conducted hierarchically using paired Wilcoxon tests with an alpha significance level of 0.05. Urinary bladder filling influenced the cervix-to-uterine angle (p < 0.001) but had no clear effect on image quality (p > 0.05). A moderately full bladder provided the best delineation of fat between the bladder and uterus (p = 0.0009). A full bladder resulted in highest ovarian displacement (p = 0.0059). Timing within the menstrual cycle did not influence the depiction of zonal anatomy (p > 0.05). Fasting (p < 0.02) and saturation bands (p < 0.001) had a positive effect on image quality. Glucagon was associated with decreased MRI artefacts (p = 0.002). Fasting, antispasmodic agents, and saturation bands improved MR image quality and are recommended for female pelvic MRI. Urinary bladder filling influenced the cervix-to-uterine angle, but had no clear effect on image quality. • Fasting, saturation band, and glucagon injection significantly reduced bowel movement artefacts. • Depiction of the anatomical details of the uterus was not influenced by the timing of MRI within the menstrual cycle. • Although bladder filling did not impact diagnostic capabilities in healthy volunteers, in clinical practice, it may be useful to examine patients with a moderately full bladder, to reduce diagnostic inaccuracies.

Evaluation of a new training program to reassure primary school teachers about glucagon injection in children with type 1 diabetes during the 2017–2018 school year

IntroductionThe prevalence of type 1 diabetes (T1D) in children is increasing. Adequate knowledge and skills of primary school staff are required to deal with children affected by T1D. We aimed to evaluate a video training program (VTP) to improve the level of confidence of teachers in administering intramuscular glucagon injection during severe hypoglycemia. The secondary goal was to improve the teachers’ theoretical knowledge. Material and methodsIn this interventional study, we submitted a VTP to all primary school teachers in the French region of Normandy who received a child with T1D during the 2017–2018 school year. The VTP began with a questionnaire focused on their confidence in performing T1D-related actions and on their theoretical knowledge. Next, we offered a 10-min video covering the main issues of T1D, which could be watched freely for a fortnight. The questionnaire was subsequently resubmitted. The level of confidence was assessed on a scale of 1 to 4. Knowledge was assessed as a score out of 20. Before–after comparisons were made using the Wilcoxon signed-rank test. Determinants of a good level of confidence and knowledge before VTP were assessed in the first questionnaires using multivariate analysis. ResultsOf 221 eligible teachers, 157 (71%) answered the first questionnaire and 77 (34.8%) answered both. The VTP significantly improved the teachers’ confidence to administer a glucagon injection (+0.36 points, P<0.001). Their theoretical knowledge was also significantly improved (+1.5 points, P<0.001). ConclusionsWe propose an original practical VTP that could be useful to improve teachers’ T1D-related self-confidence in their skills and knowledge.

Glucose transporter 2 in common carp (Cyprinus carpio L.): molecular cloning, tissue expression, and the responsiveness to glucose, insulin, and glucagon.

Glucose transporter 2 (glut2) has been studied in mammals, aves, and several fish, while the comparative studies of glut2 in common carp are still lacking. In this study, glut2 was firstly isolated and characterized from the liver of common carp. The full-length cDNA of glut2 was 2351bp with an open reading frame (ORF) of 1512bp, encoding 503 amino acids. Alignment of glut2 amino acid sequences from different species revealed that common carp glut2 showed higher sequence identity with teleosts, and lower homology with mammals and amphibians. Tissue distribution demonstrated that glut2 mRNA level was mainly expressed in liver, foregut, and midgut. To investigate the actions of glut2 on glucose metabolism, the level of glut2 mRNA was detected after intraperitoneal injection of glucose, human insulin and glucagon (100ng/g), respectively. Following glucose administration, glut2 gene expression was significantly upregulated at 3h in the foregut. However, no change was found in hepatic glut2 mRNA level, indicating that glut2 may have a role in intestinal glucose uptake rather than in the liver. Following insulin treatment, the expression of glut2 was markedly downregulated at 3h and 6h in the liver, and at 3h in the foregut, respectively. Furthermore, glut2 mRNA expression was unaffected by glucagon injection in the liver and foregut. These results suggested that the expression of glut2 regulated by pancreatic hormones was different. Taken together, our studies firstly revealed the structure of the glut2 gene and its potential functions in glucose metabolism of common carp.

Magnetic resonance imaging of glycogen using its magnetic coupling with water

Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% (n = 5) after 24 h of fasting and by 76 ± 22% (n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases.

Congenital hyperinsulinism associated with Hirschsprung\u2019s disease\u2014a report of an extremely rare case

BackgroundCongenital hyperinsulinism (CH) is a rare disease, characterized by severe hypoglycemia induced by inappropriate insulin secretion from pancreatic beta-cells in neonate and infant. Hirschsprung’s disease (HD) is also a rare disease in which infants show severe bowel movement disorder. We herein report an extremely rare case of combined CH and HD.Case presentationThe patient was a full-term male infant who showed poor feeding, vomiting, and hypotonia with lethargy on the day of birth. He was transferred to tertiary hospital after a laboratory analysis revealed hyperinsulinemic hypoglycemia. The patient showed remarkable abdominal distension without meconium defecation. An abdominal X-ray showed marked dilatation of the large bowel. He was diagnosed with CH (nesidioblastosis) associated with suspected HD. He was initially treated with an intravenous infusion of high-dose glucose with the intermittent injection of glucagon. This was successfully followed by treatment with diazoxide and octreotide (a somatostatin analog). At 8 months of age, HD was confirmed by the acetylcholinesterase staining of a rectal mucosal biopsy specimen, and a transanal pull-through operation was performed to treat HD. At 14 months of age, subtotal pancreatectomy was performed for the treatment of focal CH located in the pancreatic body. His postoperative course over the past 12 years has been uneventful without any neurologic or bowel movement disorders.ConclusionsAlthough it is extremely rare for CH to be associated with HD, associated HD should be considered when a patient with CH presents severe constipation.