Measuring Second Phase of Insulin Secretion by Components of Metabolic Syndrome

Aims. There are two phases of insulin secretion, the first (FPIS) and second phase (SPIS). In this study, we built equations to predict FPIS with metabolic syndrome (MetS) components and fasting plasma insulin (FPI).Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg) was obtained. The AIRg was considered as FPIS.Results. When MetS components were only used, the following equation was built: log (FPIS) = 1.477 − 0.119 × fasting plasma glucose (FPG) + 0.079 × body mass index (BMI) − 0.523 × high-density lipoprotein cholesterol (HDL-C). After FPI was added, the second equation was formulated: log (FPIS) = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI), which provided a better accuracy than the first one.Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice.

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Large differences in the second phase of insulin secretion by small differences in islet isolation

10.1055/s-0038-1641771 ◽

2018 ◽

Author(s):

B Gaus ◽

I Rustenbeck

Keyword(s):

Insulin Secretion ◽

Second Phase ◽

Islet Isolation

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Relative importance of first- and second-phase insulin secretion in glucose homeostasis in conscious dog. II. Effects on gluconeogenesis

Diabetes ◽

10.2337/diabetes.35.7.776 ◽

1986 ◽

Vol 35 (7) ◽

pp. 776-784 ◽

Cited By ~ 5

Author(s):

K. E. Steiner ◽

S. M. Mouton ◽

P. E. Williams ◽

W. W. Lacy ◽

A. D. Cherrington

Keyword(s):

Insulin Secretion ◽

Glucose Homeostasis ◽

Second Phase ◽

Relative Importance ◽

Conscious Dog

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Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells

Chinese Journal of Natural Medicines ◽

10.1016/s1875-5364(16)30099-1 ◽

2016 ◽

Vol 14 (11) ◽

pp. 823-834 ◽

Cited By ~ 2

Author(s):

Xiao-Meng WAN ◽

Mu ZHANG ◽

Pei ZHANG ◽

Zhi-Shen XIE ◽

Feng-Guo XU ◽

...

Keyword(s):

Metabolic Syndrome ◽

Insulin Secretion ◽

Β Cells ◽

Pancreatic Β Cells

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PWD/PhJ and WSB/EiJ Mice Are Resistant to Diet-Induced Obesity But Have Abnormal Insulin Secretion

Endocrinology ◽

10.1210/en.2011-0060 ◽

2011 ◽

Vol 152 (8) ◽

pp. 3005-3017 ◽

Cited By ~ 17

Author(s):

Katie T. Y. Lee ◽

Subashini Karunakaran ◽

Maggie M. Ho ◽

Susanne M. Clee

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Large Scale ◽

Mouse Strains ◽

Second Phase ◽

Fasting Insulin ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity And Diabetes

Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.

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Metabolic amplifying pathway increases both phases of insulin secretion independently of β-cell actin microfilaments

AJP Cell Physiology ◽

10.1152/ajpcell.00138.2010 ◽

2010 ◽

Vol 299 (2) ◽

pp. C389-C398 ◽

Cited By ~ 34

Author(s):

Nizar I. Mourad ◽

Myriam Nenquin ◽

Jean-Claude Henquin

Keyword(s):

Insulin Secretion ◽

Actin Polymerization ◽

Second Phase ◽

Actin Microfilaments ◽

Actin Depolymerization ◽

Inhibitory Function ◽

Insulin Granules ◽

Priming Process ◽

Underlying Mechanisms ◽

Amplifying Pathway

Two pathways control glucose-induced insulin secretion (IS) by β-cells. The triggering pathway involves ATP-sensitive potassium (KATP) channel-dependent depolarization, Ca2+ influx, and a rise in the cytosolic Ca2+ concentration ([Ca2+]c), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca2+]c. The underlying mechanisms are unknown. Here, we tested the hypothesis that amplification implicates actin microfilaments. Mouse islets were treated with latrunculin B and cytochalasin B to depolymerize actin or jasplakinolide to polymerize actin. They were then perifused to measure [Ca2+]c and IS. Metabolic amplification was studied during imposed steady elevation of [Ca2+]c by tolbutamide or KCl or by comparing the magnitude of [Ca2+]c and IS changes produced by glucose and tolbutamide. Both actin polymerization and depolymerization augmented IS triggered by all stimuli without increasing (sometimes decreasing) [Ca2+]c, which indicates a predominantly inhibitory function of microfilaments in exocytosis at a step distal to [Ca2+]c increase. When [Ca2+]c was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was facilitated by actin depolymerization and unaffected by polymerization. Both phases of IS were larger in response to high-glucose than to tolbutamide in low-glucose, although triggering [Ca2+]c was lower. This difference in IS, due to amplification, persisted when the IS rate was doubled by actin depolymerization or polymerization. In conclusion, metabolic amplification is rapid and influences the first as well as the second phase of IS. It is a late step of stimulus-secretion coupling, which does not require functional actin microfilaments and could correspond to acceleration of the priming process conferring release competence to insulin granules.

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Conditional expression of the FTO gene product in rat INS-1 cells reveals its rapid turnover and a role in the profile of glucose-induced insulin secretion

Clinical Science ◽

10.1042/cs20100416 ◽

2011 ◽

Vol 120 (9) ◽

pp. 403-413 ◽

Cited By ~ 15

Author(s):

Mark A. Russell ◽

Noel G. Morgan

Keyword(s):

Insulin Secretion ◽

Expression System ◽

Proteasome Inhibitors ◽

Inducible Promoter ◽

Insulin Biosynthesis ◽

Second Phase ◽

Β Cells ◽

Pancreatic Β Cells ◽

Peripheral Tissues ◽

Conditional Expression

Common polymorphisms within the FTO (fat mass and obesity-associated) gene correlate with increased BMI (body mass index) and a rising risk of Type 2 diabetes. FTO is highly expressed in the brain but has also been detected in peripheral tissues, including the endocrine pancreas, although its function there is unclear. The aim of the present study was to investigate the role of FTO protein in pancreatic β-cells using a conditional expression system developed in INS-1 cells. INS-1 cells were stably transfected with FTO–HA (haemagluttinin) incorporated under the control of a tetracycline-inducible promoter. Induction of FTO protein resulted in localization of the tagged protein to the nucleus. The level of FTO–HA protein achieved in transfected cells was tightly regulated, and experiments with selective inhibitors revealed that FTO–HA is rapidly degraded via the ubiquitin/proteasome pathway. The nuclear localization was not altered by proteasome inhibitors, although following treatment with PYR-41, an inhibitor of ubiquitination, some of the protein adopted a perinuclear localization. Unexpectedly, modestly increased expression of FTO–HA selectively enhanced the first phase of insulin secretion when INS-1 monolayers or pseudoislets were stimulated with 20 mM glucose, whereas the second phase remained unchanged. The mechanism responsible for the potentiation of glucose-induced insulin secretion is unclear; however, further experiments revealed that it did not involve an increase in insulin biosynthesis or any changes in STAT3 (signal transducer and activator of transcription 3) expression. Taken together, these results suggest that the FTO protein may play a hitherto unrecognized role in the control of first-phase insulin secretion in pancreatic β-cells.

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Effect of Gymnema sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion

Journal of Medicinal Food ◽

10.1089/jmf.2017.0001 ◽

2017 ◽

Vol 20 (8) ◽

pp. 750-754 ◽

Cited By ~ 9

Author(s):

Laura Y. Zuñiga ◽

Manuel González-Ortiz ◽

Esperanza Martínez-Abundis

Keyword(s):

Metabolic Syndrome ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Gymnema Sylvestre

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Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00624.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1775-E1781 ◽

Cited By ~ 59

Author(s):

Kenneth Cusi ◽

Sangeeta Kashyap ◽

Amalia Gastaldelli ◽

Mandeep Bajaj ◽

Eugenio Cersosimo

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Family History ◽

Second Phase ◽

Β Cell ◽

C Peptide ◽

Hyperglycemic Clamp ◽

History Of ◽

Plasma Ffa

Elevated plasma FFA cause β-cell lipotoxicity and impair insulin secretion in nondiabetic subjects predisposed to type 2 diabetes mellitus [T2DM; i.e., with a strong family history of T2DM (FH+)] but not in nondiabetic subjects without a family history of T2DM. To determine whether lowering plasma FFA with acipimox, an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine FH+ volunteers were admitted twice and received in random order either acipimox or placebo (double-blind) for 48 h. Plasma glucose/insulin/C-peptide concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates (ISRs) were assessed during a +125 mg/dl hyperglycemic clamp. Acipimox reduced 48-h plasma FFA by 36% ( P < 0.001) and increased the plasma C-peptide relative to the plasma glucose concentration or ΔC-peptide/Δglucose AUC (+177%, P = 0.02), an index of improved β-cell function. Acipimox improved insulin sensitivity (M/I) 26.1 ± 5% ( P < 0.04). First- (+19 ± 6%, P = 0.1) and second-phase (+31 ± 6%, P = 0.05) ISRs during the hyperglycemic clamp also improved. This was particularly evident when examined relative to the prevailing insulin resistance [1/(M/I)], as both first- and second-phase ISR markedly increased by 29 ± 7 ( P < 0.05) and 41 ± 8% ( P = 0.02). There was an inverse correlation between fasting FFA and first-phase ISR ( r2 = 0.31, P < 0.02) and acute (2–4 min) glucose-induced insulin release after acipimox ( r2 =0.52, P < 0.04). In this proof-of-concept study in FH+ individuals predisposed to T2DM, a 48-h reduction of plasma FFA improves day-long meal and glucose-stimulated insulin secretion. These results provide additional evidence for the important role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed to T2DM.

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Magnesium requirement for somatostatin inhibition of insulin secretion

Acta Endocrinologica ◽

10.1530/acta.0.1050083 ◽

1984 ◽

Vol 105 (1) ◽

pp. 83-86 ◽

Cited By ~ 2

Author(s):

Donald L. Curry ◽

Leslie L. Bennett

Keyword(s):

Insulin Secretion ◽

Calcium Concentration ◽

Inhibitory Effect ◽

Secretory Process ◽

Magnesium Ion ◽

Second Phase ◽

Intracellular Membrane ◽

Calcium Magnesium ◽

First Phase Insulin Secretion ◽

Insulin Secretory Response

Abstract. Rat pancreas perfusions were performed using a perfusate with a fixed calcium concentration of 5 mEq/l and magnesium varying from 0 to 0.6 mEq/dl. Insulin secretion was stimulated by a constant glucose infusion of 300 mg/dl. This glucose concentration produces the typical biphasic insulin secretory response. We observed that in the absence of magnesium, somatostatin concentrations of 0.5 and 2.0 ng/ml were without effect on first phase insulin secretion. However, these same somatostatin levels produced 50% or more inhibition of insulin secretion in the presence of magnesium at 0.3 or 0.6 mEq/l. Similarly, in the absence of magnesium, somatostatin at 50 ng/ml failed to inhibit second phase insulin secretion, whereas this same somatostatin level produced about 50% inhibition of insulin secretion in the presence of magnesium at 0.3 mEq/l. Thus, altering perfusate magnesium concentrations without changing calcium is an important determinant of the degree of inhibition of secretion produced by somatostatin. In particular, in the absence of magnesium ion, somatostatin concentrations which would 'normally' produce 50% inhibition of secretion (ID50) are without effect. Therefore, magnesium ion is necessary for the full inhibitory effect of somatostatin to occur. These results suggest that inhibitors, as well as potentiators, of the insulin secretory process may act by altering intracellular/membrane calcium-magnesium ratios, but in opposite directions.

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