scholarly journals Clinical and genetic characterization of congenital hyperinsulinism in Spain

2016 ◽  
Vol 174 (6) ◽  
pp. 717-726 ◽  
Author(s):  
R Martínez ◽  
C Fernández-Ramos ◽  
A Vela ◽  
T Velayos ◽  
A Aguayo ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Genetic Diagnosis ◽  
Clinical Information ◽  
Severe Hypoglycemia ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Design And Methods

Context Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic β-cells. Objective To characterize clinically and genetically CHI patients in Spain. Design and methods We included 50 patients with CHI from Spain. Clinical information was provided by the referring clinicians. Mutational analysis was carried out for KCNJ11, ABCC8, and GCK genes. The GLUD1, HNF4A, HNF1A, UCP2, and HADH genes were sequenced depending on the clinical phenotype. Results We identified the genetic etiology in 28 of the 50 CHI patients tested: 21 had a mutation in KATP channel genes (42%), three in GLUD1 (6%), and four in GCK (8%). Most mutations were found in ABCC8 (20/50). Half of these patients (10/20) were homozygous or compound heterozygous, with nine being unresponsive to diazoxide treatment. The other half had heterozygous mutations in ABCC8, six of them being unresponsive to diazoxide treatment and four being responsive to diazoxide treatment. We identified 22 different mutations in the KATP channel genes, of which ten were novel. Notably, patients with ABCC8 mutations were diagnosed earlier, with lower blood glucose levels and required higher doses of diazoxide than those without a genetic diagnosis. Conclusions Genetic analysis revealed mutations in 56% of the CHI patients. ABCC8 mutations are the most frequent cause of CHI in Spain. We found ten novel mutations in the KATP channel genes. The genetic diagnosis is more likely to be achieved in patients with onset within the first week of life and in those who fail to respond to diazoxide treatment.

scholarly journals Intraperitoneal insulin administration in pigs: effect on circulating insulin and glucose levels

2021 ◽  
Vol 9 (1) ◽  
pp. e001929
Author(s):  
Ilze Dirnena-Fusini ◽  
Marte Kierulf Åm ◽  
Anders Lyngvi Fougner ◽  
Sven Magnus Carlsen ◽  
Sverre Christian Christiansen
Keyword(s):  
Systemic Circulation ◽  
Subcutaneous Insulin ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Endogenous Insulin ◽  
Blood Glucose Levels ◽  
Intraperitoneal Insulin ◽  
A Minor ◽  
Design And Methods ◽  
Mean Blood Glucose

IntroductionThe effect of intraperitoneal insulin infusion has limited evidence in the literature. Therefore, the aim of the study was to investigate the pharmacokinetics and pharmacodynamics of different intraperitoneal insulin boluses. There is a lack of studies comparing the insulin appearance in the systemic circulation after intraperitoneal compared with subcutaneous insulin delivery. Thus, we also aimed for a comparison with the subcutaneous route.Research design and methodsEight anesthetized, non-diabetic pigs were given three different intraperitoneal insulin boluses (2, 5 and 10 U). The order of boluses for the last six pigs was randomized. Endogenous insulin and glucagon release were suppressed by repeated somatostatin analog injections. The first pig was used to identify the infusion rate of glucose to maintain stable glucose values throughout the experiment. The estimated difference between insulin boluses was compared using two-way analysis of variance (GraphPad Prism V.8).In addition, a trial of three pigs which received subcutaneous insulin boluses was included for comparison with intraperitoneal insulin boluses.ResultsDecreased mean blood glucose levels were observed after 5 and 10 U intraperitoneal insulin boluses compared with the 2 U boluses. No changes in circulating insulin levels were observed after the 2 and 5 U intraperitoneal boluses, while increased circulating insulin levels were observed after the 10 U intraperitoneal boluses. Subcutaneously injected insulin resulted in higher values of circulating insulin compared with the corresponding intraperitoneal boluses.ConclusionsSmaller intraperitoneal boluses of insulin have an effect on circulating glucose levels without increasing insulin levels in the systemic circulation. By increasing the insulin bolus, a major increase in circulating insulin was observed, with a minor additive effect on circulating glucose levels. This is compatible with a close to 100% first-pass effect in the liver after smaller intraperitoneal boluses. Subcutaneous insulin boluses markedly increased circulating insulin levels.

BECKWITH'S SYNDROME WITH EXTREME ORGAN HYPERPLASIA

PEDIATRICS ◽  
1973 ◽  
Vol 52 (3) ◽  
pp. 372-381
Author(s):  
Thomas F. Roe ◽  
Ann K. Kershnar ◽  
Jordan J. Weitzman ◽  
Luis Salinas Madrigal
Keyword(s):  
Adrenal Gland ◽  
Abdominal Mass ◽  
Severe Hypoglycemia ◽  
Immunoreactive Insulin ◽  
Left Adrenal Gland ◽  
Adrenal Steroid ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Pedunculated Tumor ◽  
The Right

A large newborn infant with hemihypertrophy, omphalocele, hepatomegaly, left upper quadrant abdominal mass, and zoster-like skin rash had severe hypoglycemia at 4 hours of age. Serum immunoreactive insulin levels were markedly elevated. Hypoglycemia was not controlled by vigorous medical therapy but blood glucose levels returned toward normal following subtotal excision of the markedly hyperplastic pancreas at 24 days of age. At 4½ months of age, a right upper quadrant abdominal mass was noted and urinary adrenal steroid levels were elevated. The right adrenal gland was found to be markedly hyperplastic and it was removed; the left adrenal gland was slightly hyperplastic. Between the ages of 5 and 8 months the umbilical stump enlarged progressively forming a large pedunculated tumor which was removed. This patient presents an unusually severe example of Beckwith's syndrome with both prenatal and postnatal organ overgrowth, severe hypoglycemia and hyperinsulinism.

scholarly journals Glucose-Responsive Insulin Through Bioconjugation Approaches

2019 ◽  
Vol 14 (2) ◽  
pp. 198-203 ◽  
Author(s):  
Maria M. Disotuar ◽  
Diao Chen ◽  
Nai-Pin Lin ◽  
Danny Hung-Chieh Chou
Keyword(s):  
Glycemic Control ◽  
Severe Hypoglycemia ◽  
Therapeutic Window ◽  
Insulin Analogs ◽  
Future Directions ◽  
Major Health ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucose Responsiveness ◽  
Reduced Risk

Although insulin analogs have markedly improved glycemic control for people with diabetes, glycemic excursions still cause major health problems and complications. In particular, the narrow therapeutic window of current insulin therapy makes it extremely difficult to maintain normoglycemia without risking severe hypoglycemia. Currently, there are no FDA-approved insulin therapeutics whose bioactivity is regulated by blood glucose levels. This review discusses recent progress on developing glucose-responsive insulin (GRI) bioconjugates without the need of exogenous matrices. Through this approach, tremendous efforts have been made over the years to demonstrate the promise of better glycemic control and reduced risk of hypoglycemia. Last, we discuss future directions of GRI development with a goal to maximize the glucose responsiveness.

Cryptic male choice: experimental evidence of sperm sex ratio and seminal fluid adjustment in relation to coital rate

2017 ◽  
Vol 29 (7) ◽  
pp. 1401 ◽  
Author(s):  
A. M. Edwards ◽  
E. Z. Cameron
Keyword(s):  
Sex Ratio ◽  
Seminal Fluid ◽  
Sex Ratios ◽  
Laboratory Mice ◽  
Lower Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Maternal Manipulation ◽  
Seminal Fluids

The differential allocation hypothesis suggests that a mother should adjust the sex of offspring in relation to her mate’s attractiveness, thereby increasing future reproductive fitness when her sons inherit the attractive traits. More attractive males have been shown to sire more sons, but it is possible that the sex ratio skew could be a result of paternal rather than maternal manipulation, which would be a more parsimonious explanation. We manipulated coital rate (an indicator of attractiveness) in laboratory mice and showed that males that mate more often have higher levels of glucose in their semen despite lower blood glucose levels. Since peri-conceptual glucose levels in utero increase male conceptus survival, this could result in male-biased sex ratios. The males that mated most also had more remaining X-chromosome-bearing-spermatozoa, suggesting depletion of Y-chromosome-bearing-spermatozoa during mating. We hypothesise that males may alter both seminal fluids and X : Y ratios in an ejaculate to influence subsequent sex ratios. Our results further support a paternal role in sex allocation.

scholarly journals Role of POMC and AgRP neuronal activities on glycaemia in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aykut Göktürk Üner ◽  
Onur Keçik ◽  
Paula G. F. Quaresma ◽  
Thiago M. De Araujo ◽  
Hyon Lee ◽  
...  
Keyword(s):  
Neuronal Firing ◽  
Designer Drugs ◽  
Lower Blood Glucose ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Neuronal Populations ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Stimulation Of

Abstract Leptin regulates both feeding and glycaemia primarily through its receptors expressed on agouti-related peptide (AgRP) and pro-opiomelanocortin-expressing (POMC) neurons; however, it is unknown whether activity of these neuronal populations mediates the regulation of these processes. To determine this, we injected Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) viruses into the hypothalamus of normoglycaemic and diabetic AgRP-ires-cre and POMC-cre mice to chemogenetically activate or inhibit these neuronal populations. Despite robust changes in food intake, activation or inhibition of AgRP neurons did not affect glycaemia, while activation caused significant (P = 0.014) impairment in insulin sensitivity. Stimulation of AgRP neurons in diabetic mice reversed leptin’s ability to inhibit feeding but did not counter leptin’s ability to lower blood glucose levels. Notably, the inhibition of POMC neurons stimulated feeding while decreasing glucose levels in normoglycaemic mice. The findings suggest that leptin’s effects on feeding by AgRP neurons are mediated by changes in neuronal firing, while the control of glucose balance by these cells is independent of chemogenetic activation or inhibition. The firing-dependent glucose lowering mechanism within POMC neurons is a potential target for the development of novel anti-diabetic medicines.

scholarly journals Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review

2020 ◽  
Vol 2020 ◽  
pp. 1-36 ◽  
Author(s):  
Jeremiah Oshiomame Unuofin ◽  
Sogolo Lucky Lebelo
Keyword(s):  
Side Effects ◽  
Beta Cell ◽  
Cell Function ◽  
Bioactive Molecules ◽  
Endocrine Gland ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Glucagon Like Peptide 1

Diabetes mellitus is a metabolic disorder that majorly affects the endocrine gland, and it is symbolized by hyperglycemia and glucose intolerance owing to deficient insulin secretory responses and beta cell dysfunction. This ailment affects as many as 451 million people worldwide, and it is also one of the leading causes of death. In spite of the immense advances made in the development of orthodox antidiabetic drugs, these drugs are often considered not successful for the management and treatment of T2DM due to the myriad side effects associated with them. Thus, the exploration of medicinal herbs and natural products as therapeutic sources for the treatment of T2DM is promoted because they have little or no side effects. Bioactive molecules isolated from natural sources have been proven to lower blood glucose levels via regulating one or more of the following mechanisms: improvement of beta cell function, insulin resistance, glucose (re)absorption, and glucagon-like peptide-1 homeostasis. In recent times, the mechanisms of action of different bioactive molecules with antidiabetic properties and phytochemistry are gaining a lot of attention in the area of drug discovery. This review article presents an update of the findings from clinical research into medicinal plant therapy for T2DM.

scholarly journals Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2330 ◽  
Author(s):  
Ari ◽  
Murdun ◽  
Koutnik ◽  
Goldhagen ◽  
Rogers ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Rodent Models ◽  
Lower Blood Glucose ◽  
Post Exercise ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lower Blood Glucose Level ◽  
Lower Blood

Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. Compliance to KD can be difficult, so alternative therapies that help reduce glucose levels are needed. Exogenous ketones provide an alternative method to elevate blood ketone levels without strict dietary requirements. In this study, we tested the changes in blood glucose and ketone (βHB) levels in response to acute, sub-chronic, and chronic administration of various ketogenic compounds in either a post-exercise or rested state. WAG/Rij (WR) rats, a rodent model of human absence epilepsy, GLUT1 deficiency syndrome mice (GLUT1D), and wild type Sprague Dawley rats (SPD) were assessed. Non-pathological animals were also assessed across different age ranges. Experimental groups included KD, standard diet (SD) supplemented with water (Control, C) or with exogenous ketones: 1, 3-butanediol (BD), βHB mineral salt (KS), KS with medium chain triglyceride/MCT (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS). In rested WR rats, the KE, KS, KSMCT groups had lower blood glucose level after 1 h of treatment, and in KE and KSMCT groups after 24 h. After exercise, the KE, KSMCT, KEKS, and KEMCT groups had lowered glucose levels after 1 h, and in the KEKS and KEMCT groups after 7 days, compared to control. In GLUT1D mice without exercise, only KE resulted in significantly lower glucose levels at week 2 and week 6 during a 10 weeks long chronic feeding study. In 4-month and 1-year-old SPD rats in the post-exercise trials, blood glucose was significantly lower in KD and KE, and in KEMCT groups, respectively. After seven days, the KSMCT group had the most significantly reduced blood glucose levels, compared to control. These results indicate that exogenous ketones were efficacious in reducing blood glucose levels within and outside the context of exercise in various rodent models of different ages, with and without pathology.

scholarly journals Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism

2013 ◽  
Vol 168 (4) ◽  
pp. 557-564 ◽  
Author(s):  
Ritika R Kapoor ◽  
Sarah E Flanagan ◽  
Ved Bhushan Arya ◽  
Julian P Shield ◽  
Sian Ellard ◽  
...  
Keyword(s):  
Family History ◽  
Positive Family History ◽  
Genetic Diagnosis ◽  
Clinical Information ◽  
Congenital Hyperinsulinism ◽  
Molecular Characterisation ◽  
Heterogeneous Condition ◽  
Diffuse Disease ◽  
Molecular Aspects ◽  
Inherited Mutations

BackgroundCongenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (ABCC8,KCNJ11,GLUD1,GCK,HADH,SLC16A1,HNF4AandHNF1A) are known to cause CHI.AimTo characterise the clinical and molecular aspects of a large cohort of patients with CHI.MethodologyThree hundred patients were recruited and clinical information was collected before genotyping.ABCC8andKCNJ11genes were analysed in all patients. Mutations inGLUD1,HADH,GCKandHNF4Agenes were sought in patients with diazoxide-responsive CHI with hyperammonaemia (GLUD1), raised 3-hydroxybutyrylcarnitine and/or consanguinity (HADH), positive family history (GCK) or when CHI was diagnosed within the first week of life (HNF4A).ResultsMutations were identified in 136/300 patients (45.3%). Mutations inABCC8/KCNJ11were the commonest genetic cause identified (n=109, 36.3%). Among diazoxide-unresponsive patients (n=105), mutations inABCC8/KCNJ11were identified in 92 (87.6%) patients, of whom 63 patients had recessively inherited mutations while four patients had dominantly inherited mutations. A paternal mutation in theABCC8/KCNJ11genes was identified in 23 diazoxide-unresponsive patients, of whom six had diffuse disease. Among the diazoxide-responsive patients (n=183), mutations were identified in 41 patients (22.4%). These include mutations inABCC8/KCNJ11(n=15),HNF4A(n=7),GLUD1(n=16) andHADH(n=3).ConclusionsA genetic diagnosis was made for 45.3% of patients in this large series. Mutations in theABCC8gene were the commonest identifiable cause. The vast majority of patients with diazoxide-responsive CHI (77.6%) had no identifiable mutations, suggesting other genetic and/or environmental mechanisms.

Antidiabetic Activity of Peperomia pellucida In Streptozotocin-Induced Diabetic Mice

2021 ◽  
Vol 7 (2) ◽  
pp. 120-129
Author(s):  
Sholihatil Hidayati
Keyword(s):  
Blood Glucose ◽  
Ethanol Extract ◽  
Hexane Fraction ◽  
Antidiabetic Activity ◽  
Diabetic Mice ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Potential Development ◽  
Lower Blood ◽  
Development Objectives

Background: Diabetes mellitus is a heterogeneous group of diseases in the form of disorders in the body's metabolism clinically. Peperomia pellucida herbs have phytochemical containing which is antidiabetic potential development. Objectives: This study was conducted to compare the antidiabetic activity of ethanol extract and n-hexane fraction of Peperomia pellucida. Material and Methods: This research was conducted by make diabetic mice with 50 mg/kg.bw of streptozotocin induction, which was then treated with ethanol extract and n-hexane fraction of Peperomia pellucida with doses 250 mg/kgbw for 7 days.  Results: The results showed that the ethanol extract and n-hexane fraction of Peperomia pellucida reduced blood glucose levels in diabetic mice due to streptozotocin induction. The n-hexane fraction of Peperomia pellucida can lower blood glucose levels as much 244.00 ± 18.99 mg/dL better than the ethanol extract, which is 99.50 ± 28.17 mg/dL. Conclusions: Peperomia pellucida herb has the potential to be developed as an antidiabetic agent.

Chloroplast thylakoids reduce glucose uptake and decrease intestinal macromolecular permeability

2011 ◽  
Vol 106 (6) ◽  
pp. 836-844 ◽  
Author(s):  
Caroline Montelius ◽  
Karolina Gustafsson ◽  
Björn Weström ◽  
Per-Åke Albertsson ◽  
Sinan Cem Emek ◽  
...  
Keyword(s):  
Oral Intake ◽  
Thylakoid Membranes ◽  
Ussing Chambers ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Sterical Hindrance ◽  
Macromolecular Permeability ◽  
Dose Dependent

Thylakoid membranes, derived from chloroplasts, have previously been shown to retard fat digestion and lower blood glucose levels after oral intake. The purpose of the present study was to investigate the effect of thylakoid membranes on the passage of methyl-glucose, dextran and ovalbumin over rat intestine in vitro using Ussing chambers. The results show that thylakoids retard the passage of each of the test molecules in a dose-dependent way. The thylakoids appear to be attached on the mucosal surface and a mechanism is suggested that the thylakoids delay the passage of the test molecules by sterical hindrance. The present results indicate that thylakoid membranes may be useful both to control intestinal absorption of glucose and to enhance the barrier function of the intestine.

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