Intravenous Glucose Infusion Research Articles

Circulating Obestatin Concentration is Lowered by Insulin in Rats

Circulating obestatin is lowered by food intake, but factors involved in obestatin regulation remain unclear. The aim of this study was to determine whether intravenous glucose or insulin infusion lowers obestatin. Rats were infused over 3 h with either A. saline (controls); B. dextrose to steady state blood glucose ~16.7 mM, or C. insulin 7.5 mU/kg.min, plus dextrose as needed to clamp to euglycemic basal concentrations. During 3 h of infusion, group B had significantly greater (P<0.01) glucose, 18.75±1.27 mM, than groups A (6.10±0.33 mM) or C (6.19±0.18 mM). Groups B and C had hyperinsulinemia at the end of the 3 h infusion (1.02±0.03 ng/ml, 1.07±0.02 ng/ml) compared with saline-infused (0.38±0.01 ng/ml, P<0.01). Obestatin concentrations were significantly reduced (P<0.01) in both hyperinsulinemic groups and (B=0.95±0.06 ng/ml; C=0.87±0.04 ng/ml) versus controls (1.56±0.13 ng/ml). These data suggest that insulin can decrease the plasma obestatin levels.

Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses

Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4) and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039±0.0012 mmol/kg/min and M-to-I ratio (100×) 0.014±0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7±0.78 mmol/L) and hyperinsulinaemia (208±26.1 μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e., laminitis) in horses may be at or below a serum concentration of ∼200 μIU/mL.

Incretin effect: GLP-1, GIP, DPP4

The term incretin effect was used to describe the fact that oral glucose load produces a greater insulin response than that of an isoglycemic intravenous glucose infusion. This difference has been attributed to gastrointestinal peptides GLP-1 and GIP. Since incretin effect is reduced in subjects with type 2 diabetes, despite GLP-1 activity preservation, two forms of incretin-based treatment have emerged: GLP-1R agonists, administered subcutaneously and DPP-4 inhibitors, administered orally. There is a great interest whether incretin-based treatment will be associated with sustained long-term control and improvement in β-cell function. The observation that GLP-1R agonists improve myocardial function and survival of cardiomyocytes highlights the need for further studies. Incretin-based therapies offer a new option and show great promise for the treatment of type 2 diabetes.

Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health

Two new formulations, respectively denominated INT_M1 and INT_M2, of an integrated mathematical model to describe the glycemic and insulinemic responses to a 75g oral glucose tolerance test (OGTT) are proposed and compared. The INT_M1 assumes a single compartment for the intestine and the derivative of a power exponential function for the gastric emptying rate, while, in the INT_M2, a nonlinear three-compartment system model is adopted to produce a more realistic, multiphase gastric emptying rate. Both models were implemented in a Matlab-based, two-step procedure for estimation of seven adjustable coefficients characterizing the gastric emptying rate and the incretin, insulin and glucose kinetics. Model behaviour was tested vs. mean plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucose and insulin measurements from two different laboratories, where glycemic profiles observed during a 75g OGTT were matched in healthy subjects (HC1- and HC2-group, respectively) by means of an isoglycemic intravenous glucose (I-IVG) infusion. Under the hypothesis of an additive effect of GLP-1 and GIP on insulin potentiation, our results demonstrated a substantial equivalence of the two models in matching the data. Model parameter estimates showed to be suitable markers of differences observed in the OGTT and matched I-IVG responses from the HC1-group compared to the HC2-group. Model implementation in our two-step parameter estimation procedure enhances the possibility of a prospective application for individualization of the incretin effect in a single subject, when his/her data are plugged in.

In Silico Evaluation of Glucose Control Protocols for Critically Ill Patients

This letter presents an in silico evaluation method of glucose control protocols for critically ill patients with hyperglycemia. Although various glucose control protocols were introduced and investigated in clinical trials, development and validation of a novel glucose control protocol for critically ill patients require too much time and resources in clinical evaluation. We employed a virtual patient model of the critically ill patient with hyperglycemia and evaluated the clinically investigated glucose control protocols in a computational environment. The three-day simulation results presented the time profiles of glucose and insulin concentrations, the amount of enteral feed and intravenous bolus of glucose, and the intravenous insulin infusion rate. The hyperglycemia and hypoglycemia index, blood glucose concentrations, insulin doses, intravenous glucose infusion rates, and glucose feed rates were compared between different protocols. It is shown that a similar hypoglycemia incidence exists in simulation and clinical results. We concluded that this in silico simulation method using a virtual patient model could be useful for predicting hypoglycemic incidence of novel glucose control protocols for critically ill patients, prior to clinical trials.

Changes in Differential Functional Magnetic Resonance Signals in the Rodent Brain Elicited by Mixed-Nutrient or Protein-Enriched Meals

The hypothalamus and brain stem have important roles in regulating food intake; the roles of other nonhomeostatic centers in detecting nutrient content of ingested food have been poorly characterized. We used blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) to map brain regions that are responsive to intragastric infusion of isocaloric amounts of a mixed nutrient or protein, and assessed the role of blood glucose in the observed BOLD signal changes. Brain images were acquired, using a 9.4 T MRI system, from anesthetized rats during intragastric infusion of saline (n = 7), or 12 kcal of a mixed nutrient (n = 13) or protein (n = 6). Nutrient-induced changes in blood parameters and the effects of intravenous infusion of saline or glucose (n = 5/treatment) on BOLD fMRI signal changes were also evaluated. Intragastric nutrient infusion reduced the BOLD fMRI signal intensity in homeostatic (hypothalamus, nucleus tractus solitarius) and nonhomeostatic (thalamus, hippocampus, caudate putamen, cerebral cortex, cerebellum) centers; these effects were mimicked qualitatively by intravenous glucose. In contrast to a mixed meal, protein load reduced the BOLD fMRI signal in the amygdala. BOLD fMRI signal changes were inversely correlated with circulating concentrations of amylin, insulin, peptide YY, and glucagon-like peptide-1. The caloric content of a meal is signaled from the gut to the brain and affects activity in homeostatic and non-homeostatic centers; blood glucose concentrations have an important role. The satiety effects of protein are associated with activity changes specifically in the amygdala.

Methylmalonic acidemia and hyperglycemia: An unusual association

Introduction: Hyperglycemia is an exceptional manifestation of methylmalonic acidemia (MMA). We describe a patient with MMA in whom we observed a hyperglycemia which improved under treatment of the metabolic crisis. Case report: A 14 month-old boy presented with an acute generalized dystonia and lethargy preceded by fever, vomiting and lethargy at the age of 13 months. Biological investigations showed a hyperglycemia, a lactic acidosis and a hyperammonemia. Urinary organic acid analysis showed accumulation of methylmalonic acid, tiglylglycine and methylcitrate leading to the diagnosis of MMA. The patient underwent symptomatic treatment with rapid improvement of general condition, consciousness and gradual normalization of biological parameters especially glycemia after 6 days without using insulinotherapy. Discussion: MMA is an autosomal recessive disorder caused by a deficiency of methylmalonyl-CoA mutase resulting in methylmalonic acid accumulation. Biochemically, the disorder is typically characterized by: metabolic acidosis, ketonemia or ketonuria, hyperammonemia, leukopenia, thrombocytopenia and anemia. Hypoglycemia is a frequent manifestation of MMA. Our patient presented a hyperglycemia, which is unusual in MMA, since we found only three patients reported with this association. Pathophysiology remains unknown. In reported cases, hyperglycemia was treated by insulin therapy and reducing glucose intravenous infusion, with fatal outcome. In our patient glycemia spontaneously normalized after treatment of the metabolic crisis. Conclusion: Hyperglycemia is an exceptional manifestation of MMA and could be a seriousness marker.

A 4-h hyperglycaemic excursion induces rapid and slow changes in major electrolytes in blood in healthy human subjects

Hyperglycaemia is well known to cause reductions in plasma Na(+) levels or even hyponatraemia due to an osmotically induced dilution of the interstitium and blood. It is, however, unclear whether this dilution is significantly counteracted by ion regulatory homeostatic mechanism(s) or not. Furthermore, the effects of moderate hyperglycaemia on other major ions are less well known. To further clarify these questions, we measured the changes in blood osmolarity and concentrations of Na(+), K(+), Cl(-), Mg(2+) and Ca(2+) during a 4-h-long experimental hyperglycaemia in healthy subjects rendered temporarily insulin deficient using the hyperglycaemic clamp. Hyperglycaemia, 16.8 mM, was rapidly imposed from a baseline of 4.4 mM by intravenous somatostatin and glucose infusions in 19 healthy subjects (10 m, 9 f; age 36 ± 5 years (mean ± SD); BMI 22.7 ± 2.9 kg/m(2)). Subsequently, glycaemia was returned to basal and measurements continued until all dynamic changes had stopped (at ~8 h). Osmolarity increased from 281.8 ± 0.7 to 287.9 ± 0.7, while Na(+) decreased from 143.9 ± 0.3 to 138.7 ± 0.2, Cl(-) from 101.7 ± 0.2 to 99.5 ± 0.1, Ca(2+) from 1.98 ± 0.04 to 1.89 ± 0.02 and Mg(2+) from 0.84 ± 0.01 to 0.80 ± 0.00 mM. All these changes were rapidly reaching stable levels. K(+) increased from 4.02 ± 0.02 to 4.59 ± 0.02 mM (P < 0.0001) also reaching stable levels but with some delay. Na(+), Cl(-), Mg(2+) and Ca(2+) are essentially determined by blood dilution, and their values will remain diminished as long as the hyperglycaemia lasts. Partial suppression of insulin-stimulated Na(+)/K(+) pumping lead to increased K(+) levels. The combination of elevated K(+) and decreased Mg(2+) and Ca(2+) levels may lead to an altered excitability, which is particularly relevant for diabetic patients with heart disease.

Factors affecting the antidiuretic actions of the 18-monoacetate of (+)-aldosterone and of a substance secreted by eart muscle, in rats.

Abstract The method for the assay of a steroid-like substance secreted by the heart (HS) in terms of the biological activity of the 18-monoacetate of (+)-aldosterone (18MA) has been improved. Rats were equipped with ascending carotid, descending external jugular and bladder polyethylene cannulae and the urethra was ligated, under pentobarbitone anaesthesia, 24–36 h before use. Assays were made in restrained animals during sustained water diuresis induced by an intravenous infusion of glucose, 5%, and NaCl, 0&amp;#x006d;̇9%; 2: 1 at 9 mlh−1. Antidiuretic responses (measured as the area under the curve) to ascending carotid injections of 18MA and of HS, made at 0&amp;#x006d;̇01 ml s−1, maximum 15 s, were obtained from single dilutions of HS and 18MA: urine flow per min was recorded from drop (0&amp;#x006d;̇025 ml) counters. Denervation of the carotid sinus above the carotid cannula did not influence the antidiureses. Data obtained were analysed by normal statistical procedures. Ascending carotid injections of 18MA and HS did not influence mean systemic arterial pressures, the clearances of creatinine and of PAH or the urinary outputs of Na+ and K+. The antidiuresis produced was compatible with the release of ADH by HS and by 18MA. Marked seasonal variations in threshold sensitivity to 18MA and in the slopes of the log dose-effect curves for the antidiuretic actions of 18MA are described. Variations both in the threshold sensitivity and in the log dose-effect curves for the anti-diuresis caused by 18MA occur between rats of different strains.

The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves β-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 μg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic β cells, mainly increasing their proliferation and survival, should be investigated in cats.

Psyllium Lowers Blood Glucose and Insulin Concentrations in Horses

A total of 16 mature healthy horses (body weight: 515.3 ± 37 kg [mean ± SD]) were used in two experiments to determine (1) how psyllium affects postprandial blood glucose and insulin concentrations, and (2) how psyllium affects blood glucose and insulin concentrations after an intravenous glucose infusion. Psyllium was fed along with a grain and hay ration (given twice daily) for 60 days. Treatments were as follows: (1) 90 g psyllium/d, (2) 180 g psyllium/d, (3) 270 g psyllium/d, (4) an isocaloric, no supplemental psyllium control. Pre- and postprandial blood samples were collected on day 60 for experiment 1, and blood samples collected before and after intravenous glucose infusion were analyzed for experiment 2. In experiment 1, horses fed with psyllium for 60 days had lower (P < .01) mean postprandial blood glucose concentrations and there was a treatment × time effect for glucose (P < .001) and insulin (P = .03). Plasma glucose was lower at 90 minutes (P = .05) and 120 minutes (P < .001) after a meal in horses fed with psyllium as compared with an isocaloric control. Postprandial serum insulin concentrations were lower at 90 minutes (P = .002) and 300 minutes (P < .001) after a meal in horses fed with psyllium as compared with an isocaloric control. In experiment 2, peak glucose concentrations were lower (P = .01) in horses fed with psyllium for the previous 60 days compared with untreated horses and there was a treatment by time effect for glucose (P = .05). Peak blood glucose response was lower (P = .01) in horses fed with psyllium as compared with an isocaloric control after intravenous glucose infusion, whereas peak insulin concentrations and average insulin concentrations remained similar. Psyllium fed daily for 60 days alters postprandial glycemia and insulinemia in normal, nonobese, and unexercised horses.

The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of glucagon during the first 30 min of the IIGI (day B) were observed. The glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a glucagon response in the midrange between the glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase glucagon secretion.

The incretin effect in cats: comparison between oral glucose, lipids, and amino acids

Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose ( P = 0.038), but insulin concentrations were not significantly different ( P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids ( P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid ( P < 0.001) and amino acids ( P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose ( P = 0.001), amino acids ( P < 0.001), or lipids ( P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is minimal in cats and is mediated by GLP-1 but not GIP.

Peptides from adipose tissue in monitoring energy balance in infants

Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake. Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Activity of hepatic but not skeletal muscle carnitine palmitoyltransferase enzyme is depressed by intravenous glucose infusions in lactating dairy cows*

A positive energy balance in dairy cows pre-partum may decrease hepatic carnitine palmitoyltransferase (CPT) enzyme activity, which might contribute to disturbances of lipid metabolism post-partum. The purpose of this study was to investigate whether skeletal muscle CPT activity can also be downregulated during positive energy balance. Mid-lactating dairy cows were maintained on intravenous infusion of either saline (control) or glucose solutions that increased linearly over 24 days, remained at the 24-day level until day 28 and were suspended thereafter. Liver and skeletal muscle biopsies, as well as four diurnal blood samples, were taken on days 0, 8, 16, 24, and 32, representing infusion levels equivalent to 0%, 10%, 20%, 30% and 0% of the net energy for lactation (NE(L)) requirement respectively. Glucose infusion increased serum insulin concentrations on day 16 and 24 while plasma glucose levels were increased at only a single time point on day 24. Serum beta-hydroxybutyric acid concentrations decreased between day 8 and 24; whereas changes in non-esterified fatty acids were mostly insignificant. Total lipid contents of liver and skeletal muscle were not affected by treatment. Hepatic CPT activity decreased with glucose infusion (by 35% on day 24) and remained decreased on day 32. Hepatic expression levels of CPT-1A and CPT-2 mRNA were not significantly altered but tended to reflect the changes in enzyme activity. In contrast to the liver, no effect of glucose infusion was observed on skeletal muscle CPT activity. We conclude that suppression of CPT activity by positive energy balance appears to be specific for the liver in mid-lactating dairy cows.

Glucose Mediated Regulation of Beta Cell Proliferation

The pancreatic beta cell, as the sole source of circulating insulin, is indispensible for normal glucose metabolism. All forms of diabetes are characterized by insufficient insulin to meet metabolic needs, and inadequate beta cell mass is present in most forms of diabetes. Beta cell regenerative therapies provide one potential avenue for the prevention or cure of diabetes. Study of the pathways and mechanisms involved in endogenous beta cell proliferation can provide important clues to how regeneration occurs. Glucose is one important regulator of beta cell replication. Here we review the published literature investigating the effect of glucose on beta cell proliferation, and then describe the data supporting various known mechanisms of action. First, in vitro studies on fetal and adult beta cells from rodents and humans are reviewed. Next, we review evidence that circulating blood glucose regulates beta cell proliferation in living animals. These studies encompass a variety of in vivo models, including dietary manipulation, partial pancreatectomy, intravenous infusion of glucose, islet transplantation, and studies on diabetic hyperglycemia. Finally, mechanistic studies, both in vitro and in vivo, point to several different mitogenic pathways activated by glucose. Especially prominent are insulin signaling pathway members, glucose metabolism, and glucose impact on signaling by other growth factors. Multiple unanswered questions remain, and are highlighted throughout. With today's technologies we can now address questions first raised in the early 1900s, and hopefully develop new approaches to assuage the devastation of clinical diabetes.

Focal congenital hyperinsulinism in a patient with septo-optic dysplasia

An infant diagnosed as having hypopituitarism and on adequate hydrocortisone replacement therapy was referred to a tertiary endocrine unit at 5 weeks of age with persistent hypoglycemia that required a high rate of intravenous glucose infusion (up to 18 mg/kg•min⁻¹) to maintain euglycemia. A controlled hypoglycemia screen was performed to measure levels of plasma glucose, insulin, C-peptide and 3-β-hydroxybutyrate concentrations. The pancreas was analyzed by fluorine-18-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET scan. Genetic analyses were performed on the peripheral blood leukocytes, and loss of heterozygosity within the resected focal lesion of the pancreas was investigated by microsatellite analysis. A glucagon stimulation test helped determine pituitary function, and an MRI of the brain and pituitary gland was performed to define the anatomy of the intracranial structures and the pituitary gland. Focal form of congenital hyperinsulinism localized to the head of the pancreas, septo-optic dysplasia and pituitary hormone deficiencies. Resection of the focal lesion from the head of the pancreas and hormonal replacement therapy for hypopituitarism.

Glucose-Stimulated Insulin Secretion in Gastric Bypass Patients with Hypoglycemic Syndrome: No Evidence for Inappropriate Pancreatic β-cell Function

Roux-en-Y gastric bypass surgery (RYGB) has been associated with a hypoglycemic syndrome characterized by postprandial hypoglycemia and hyperinsulinemia. The syndrome is believed to occur due to insulin hypersecretion from either pancreatic beta-cell hyperplasia or hyperfunction. Eight RYGB patients with hypoglycemic syndrome had insulin secretion rates determined during a 240-min graded intravenous glucose infusion. They were compared to 34 nondiabetic, nonsurgical individuals who were divided based on their insulin sensitivity status as measured by the insulin suppression test: insulin-sensitive (n = 8), insulin intermediate (n = 7), and insulin-resistant (n = 19). RYGB patients had insulin concentrations and HOMA-IR similar to the insulin-sensitive reference group. In addition, integrated insulin secretion rates were comparable to the insulin-sensitive group and significantly lower than the insulin intermediate (p <or= 0.046) and insulin-resistant groups (p <or= 0.001). Pancreatic beta-cell sensitivity to glucose (slope relating glucose and ISR) was lowest in the RYGB group (p <or= 0.04). Patients with hypoglycemic syndrome post-RYGB do not have generalized hypersecretion of insulin and appear to have appropriate insulin secretion rate in response to intravenous glucose.

A neonatal‐onset succinyl‐CoA:3‐ketoacid CoA transferase (SCOT)‐deficient patient with T435N and c.658‐666dupAACGTGATT p.N220_I222dup mutations in the OXCT1 gene

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. Here, we report a Japanese case of neonatal-onset SCOT deficiency. The male patient presented a severe ketoacidotic crisis, with blood pH of 7.072 and bicarbonate of 5.8 mmol/L at the age of 2 days and was successfully treated with intravenous infusion of glucose and sodium bicarbonate. He was diagnosed as SCOT deficient by enzymatic assay and mutation analysis. At the age of 7 months, he developed a second ketoacidotic crisis, with blood pH of 7.059, bicarbonate of 5.4 mmol/L, and total ketone bodies of 29.1 mmol/L. He experienced two milder ketoacidotic crises at the ages of 1 year and 7 months and 3 years and 7 months. His urinary ketone bodies usually range from negative to 1+ but sometimes show 3+ (ketostix) without any symptoms. Hence, this patient does not show permanent ketonuria, which is characteristic of typical SCOT-deficient patients. He is a compound heterozygote of c.1304C > A (T435N) and c.658-666dupAACGTGATT p.N220_I222dup. mutations in the OXCT1 gene. The T435N mutation was previously reported as one which retained significant residual activity. The latter novel mutation was revealed to retain no residual activity by transient expression analysis. Both T435N and N220_I222 lie close to the SCOT dimerization interface and are not directly connected to the active site in the tertiary structure of a human SCOT dimer. In transient expression analysis, no apparent interallelic complementation or dominant negative effects were observed. Significant residual activity from the T435N mutant allele may prevent the patient from developing permanent ketonuria.

Postpartales Insulinom

A 42-year-old woman was found by her husband with unconsciousness and seizure at night three weeks after delivery of her fifth child. At a blood glucose level of 25 mg/dl, she received an intravenous infusion of glucose by the called emergency physician, leading to a rapid improvement of her symptoms. The following examination showed a low basal blood glucose level as well as pathological levels of insulin and C-peptide. These findings together with the Whipple trias (hypoglycaemia, neurological symptoms and rapid improvement after infusion of glucose) were highly suspicious of an insulinoma. Whereas CT, MRI and DOTATOC-PET were negative, endoscopic ultrasound showed a mass of 13 mm in the tail of the pancreas. The tumour was resected from the tail of the pancreas by laparoscopic enucleation. Histological examination revealed an endocrine tumour (insulinoma) of the pancreas. Postoperative blood glucose levels were within the normal range. The patient and her healthy newborn child could be dismissed from hospital on the third day after surgery. Despite its rarity, an insulinoma represents an important differential diagnosis of hypoglycaemia during and right after pregnancy.