Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics

1.Glucagon-like peptide-1 (7-36) amide (GLP-1) is released into the circulation after meals and is the most potent physiological insulinotropic hormone in man. GLP-1 has the advantages over other therapeutic agents for Type 2 diabetes of also suppressing glucagon secretion and delaying gastric emptying. One of the initial abnormalities of Type 2 diabetes is the loss of the first-phase insulin response, leading to postprandial hyperglycaemia. 2.To investigate the therapeutic potential of GLP-1 in Type 2 diabetes, six patients were entered into a 6-week, double-blind crossover trial during which each received 3 weeks treatment with subcutaneous GLP-1 or saline, self-administered three times a day immediately before meals. A standard test meal was given at the beginning and end of each treatment period. 3.GLP-1 reduced plasma glucose area under the curve (AUC) after the standard test meal by 58% (AUC, 0–240 ;min: GLP-1 start of treatment, 196±141 ;mmol·min-1·l-1; saline start of treatment, 469±124 ;mmol·min-1·l-1; F = 16.4, P< 0.05). The plasma insulin excursions were significantly higher with GLP-1 compared with saline over the initial postprandial 30 ;min, the time period during which the GLP-1 concentration was considerably elevated. The plasma glucagon levels were significantly lower over the 240-min postprandial period with GLP-1 treatment. The beneficial effects of GLP-1 on plasma glucose, insulin and glucagon concentrations were fully maintained for the 3-week treatment period. 4.We have demonstrated a significant improvement in postprandial glycaemic control with subcutaneous GLP-1 treatment. GLP-1 improves glycaemic control partially by restoring the first-phase insulin response and suppressing glucagon and is a potential treatment for Type 2 diabetes.

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Hypothalamic obesity in female rats in absence of vagally mediated hyperinsulinemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1980.239.6.e437 ◽

1980 ◽

Vol 239 (6) ◽

pp. E437-E441 ◽

Cited By ~ 1

Author(s):

B. M. King ◽

G. R. Phelps ◽

L. A. Frohman

Keyword(s):

Fasting Glucose ◽

Insulin Response ◽

Female Rats ◽

Oral Glucose ◽

Fasting Insulin ◽

Hypothalamic Obesity ◽

Glucose Levels ◽

Rapid Absorption ◽

Intact Rats

In order to assess the role of vagally mediated hyperinsulinemia in hypothalamic obesity, plasma insulin and glucose levels were assayed in vagotomized and sham-vagotomized female rats after a 6-h fast and after a measured glucose meal both before and 10–14 days after ventromedial hypothalamic (VMH) lesions. Both groups displayed similar gains in body weight in the first 10 days after VMH lesions, but only the sham-vagotomized VMH-lesioned animals displayed elevated fasting insulin levels. Fasting glucose levels did not differ either before or after the lesion. The insulin response to oral glucose was increased in VMH rats, both in vagotomized and sham-vagotomized animals, and it is concluded that the hyperresponsiveness to oral glucose is independent of vagal mediation. Vagotomy markedly exaggerated the glucose and insulin response to oral glucose loading in both intact rats and rats with VMH lesions, probably as a result of more rapid absorption of glucose from the intestine. It is concluded that the fasting hyperinsulinemia that is characteristic of VMH animals is under vagal control and that its elimination does not prevent the development of obesity.

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Decreased First Phase Insulin Response in Children with Congenital Insensitivity to Pain with Anhidrosis

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2005.18.9.873 ◽

2005 ◽

Vol 18 (9) ◽

Cited By ~ 3

Author(s):

R. Schreiber ◽

J. Levy ◽

N. Loewenthal ◽

V. Pinsk ◽

E. Hershkovitz

Keyword(s):

Insulin Response ◽

Congenital Insensitivity ◽

Congenital Insensitivity To Pain ◽

First Phase Insulin Response ◽

Insensitivity To Pain

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Normal values of first-phase insulin response to intravenous glucose in healthy Italian children and adolescents

Diabetologia ◽

10.1007/bf00418358 ◽

1996 ◽

Vol 39 (3) ◽

pp. 370-371 ◽

Cited By ~ 11

Author(s):

R. Lorini

Keyword(s):

Children And Adolescents ◽

Normal Values ◽

Insulin Response ◽

Intravenous Glucose ◽

Italian Children ◽

First Phase Insulin Response

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EVALUATION OF THE DOUBLE ANTIBODY RADIOIMMUNOASSAY OF INSULIN AND THE DETERMINATION OF INSULIN IN PLASMA AND URINE IN NORMAL SUBJECTS

Acta Endocrinologica ◽

10.1530/acta.0.0600327 ◽

1969 ◽

Vol 60 (2) ◽

pp. 327-351 ◽

Cited By ~ 17

Author(s):

Kai R. Jørgensen

Keyword(s):

Extreme Values ◽

Degradation Products ◽

Insulin Response ◽

Normal Subjects ◽

Precipitation Reaction ◽

Fasting Insulin ◽

Double Antibody ◽

Insulin In Plasma ◽

The Subject

ABSTRACT The use of the double antibody method for radio-immunological determination of insulin in plasma was evaluated on the basis of dilution and recovery experiments, as well as by the investigation of the reproducibility and accuracy of the method. Given the optimum conditions for the precipitation reaction, the method appears from the present investigations to be well suited for plasma insulin determinations. With the technique used for the separation of free and antibody bound insulin, the results of the insulin determination were found to be independent of the radioactive degradation products present in the tracer insulin. It was not possible to demonstrate any increased degradation of the tracer insulin by incubation in plasma or urine as compared with incubation in 0.5 % human albumin buffer. The absolute insulin values were found to be independent of the length of the incubation period. No difference was found between the fasting insulin concentrations in a group of new-born infants of non-diabetic mothers and a group of adult normal subjects. Similarly, the fasting insulin values were found to be independent of the sex of the subject investigated. After oral administration of glucose a considerable variation was found in the insulin response in a group of normal subjects. This variation, within the weight limits used, was found to be independent of the sex, age and weight of the subject investigated. A corresponding condition was found to be valid for the insulin excretion in the urine of normal subjects. It was concluded that the large variation in the insulin response in a group of normal subjects did not allow conclusions about the clinical significance of the extreme values, but that the variation alone must be taken as an expression for a pronounced biological variation.

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Insulin-like growth factor binding protein-1 as a predictor of glucose-stimulated hyperinsulinemia in prepubertal obese children

Acta Endocrinologica ◽

10.1530/eje.0.1400231 ◽

1999 ◽

pp. 231-234 ◽

Cited By ~ 15

Author(s):

H Saitoh ◽

T Kamoda ◽

S Nakahara ◽

T Hirano ◽

A Matsui

Keyword(s):

Growth Factor ◽

Serum Level ◽

Binding Protein ◽

Serum Insulin ◽

Insulin Response ◽

Oral Glucose ◽

Insulin Like Growth Factor ◽

Fasting Insulin ◽

Obese Children ◽

Factor Binding

OBJECTIVE: The present study was undertaken to examine the association of a glucose-stimulated insulin response with the fasting insulin-like growth factor-binding protein (IGFBP)-1 concentration in prepubertal obese children. SUBJECTS AND METHODS: The fasting levels of serum insulin and IGFBP-1 were measured in 17 obese and 16 control children. Furthermore, we performed an oral glucose tolerance test in obese children and examined the association of the area under the curve (AUC) for insulin with the fasting IGFBP-1 level. RESULTS: The mean serum level of IGFBP-1 was significantly lower in obese children (41.0 +/- 4.8 micrograms/l. P < 0.005) than in controls (91.2 +/- 9.9 micrograms/l). Although there was an inverse relationship between the fasting levels of serum insulin and IGFBP-1 in all subjects (r = -0.42, P < 0.05), no significant correlation between these two parameters was observed in the obese group alone. In obese children, the fasting IGFBP-1 level correlated inversely with AUC-insulin (r = -0.70, P < 0.005), whereas there was no significant relationship between the fasting insulin level and AUC-insulin. CONCLUSION: The present study suggests that the serum level of IGFBP-1 may be an early predictor of insulin resistance in prepubertal obesity.

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First-Phase Insulin Response to Intravenous Glucose in Cystic Fibrosis Patients with Different Degrees of Glucose Tolerance

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.1994.7.1.13 ◽

1994 ◽

Vol 7 (1) ◽

Cited By ~ 12

Author(s):

D. Cucinotta ◽

F. De Luca ◽

T. Arrigo ◽

A. Di Benedetto ◽

C. Sferlazzas ◽

...

Keyword(s):

Cystic Fibrosis ◽

Glucose Tolerance ◽

Insulin Response ◽

Intravenous Glucose ◽

First Phase Insulin Response

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TWO ABNORMALITIES OF GLUCOSE-INDUCED INSULIN SECRETION: DOSE-RESPONSE CHARACTERISTICS AND INSULIN SENSITIVITY

Acta Endocrinologica ◽

10.1530/acta.0.0920148 ◽

1979 ◽

Vol 92 (1) ◽

pp. 148-165 ◽

Cited By ~ 15

Author(s):

R. C. Turner ◽

E. Harris ◽

M. Ounsted ◽

C. Ponsford

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Insulin Response ◽

Β Cells ◽

Normal Range ◽

Response Characteristics ◽

Abnormal Metabolism ◽

Β Cell Function ◽

First Phase Insulin Response ◽

Secretory Capacity

ABSTRACT To characterize the defect of insulin secretion in diabetes, the response to different iv glucose loads has been studied in women who have had gestational diabetes and are, by definition, latent diabetic (LD). Women who have produced a large-for-dates baby, but who were not known to have been diabetic (LFD), have been investigated to determine if they have abnormal metabolism. Both groups were found to have raised fasting plasma glucose concentrations. Only the LD had glucose intolerance, which was associated with a reduced first phase insulin response to all glucose loads with a decreased maximal secretory capacity (low V max). The LFD women appeared to include a distinct abnormality in which the β cells had decreased sensitivity to glucose (high Km), with diminished secretory response to small but normal response to large loads. Whereas the LD probably have disordered μ cell function, some of the LFD women may represent the upper end of the normal range of the glucose "set" of β cell function. Neither group had insulin resistance, as measured by the hypoglycaemic response to an iv insulin bolus. A woman who has produced a LFD, but who was not known to be diabetic, does not necessarily have a diabetic tendency.

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Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-02040 ◽

2017 ◽

Vol 103 (8) ◽

pp. 2870-2878 ◽

Cited By ~ 3

Author(s):

Maarit K Koskinen ◽

Johanna Lempainen ◽

Eliisa Löyttyniemi ◽

Olli Helminen ◽

Anne Hekkala ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Response ◽

Class Ii ◽

Islet Autoantibodies ◽

Islet Autoimmunity ◽

Intravenous Glucose ◽

Hla Dr ◽

Hla Genotype ◽

First Phase Insulin Response

Abstract Context A declining first-phase insulin response (FPIR) is characteristic of the disease process leading to clinical type 1 diabetes. It is not known whether reduced FPIR depends on class II human leukocyte antigen (HLA) genotype, islet autoimmunity, or both. Objective To dissect the role of class II HLA DR-DQ genotypes and biochemical islet autoantibodies in the compromised FPIR. Design, Setting, Participants A total of 438 children with defined HLA DR-DQ genotype in the prospective Finnish Type 1 Diabetes Prediction and Prevention Study were analyzed for FPIR in a total of 1149 intravenous glucose tolerance tests and were categorized by their HLA DR-DQ genotype and the number of biochemical islet autoantibodies at the time of the first FPIR. Age-adjusted hierarchical linear mixed models were used to analyze repeated measurements of FPIR. Main Outcome Measure The associations between class II HLA DR-DQ genotype, islet autoantibody status, and FPIR. Results A strong association between the degree of risk conferred by HLA DR-DQ genotype and positivity for islet autoantibodies existed (P < 0.0001). FPIR was inversely associated with the number of biochemical autoantibodies (P < 0.0001) irrespective of HLA DR-DQ risk group. FPIR decreased over time in children with multiple autoantibodies and increased in children with no biochemical autoantibodies (P < 0.0001 and P = 0.0013, respectively). Conclusions The class II HLA DR-DQ genotype association with FPIR was secondary to the association between HLA and islet autoimmunity. Declining FPIR was associated with positivity for multiple islet autoantibodies irrespective of class II HLA DR-DQ genotype.

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