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PubMed2004

Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes.

To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan, insulin secretion and insulin sensitivity were compared across the range of glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to the criteria of the World Health Organization (WHO). We examined insulin secretion and insulin sensitivity using fasting blood glucose and insulin levels and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI) composite for insulin sensitivity. Although insulin resistance plays an important role in the development of diabetes in many ethnic populations, the differences in insulin sensitivity between NGT and IGT and between IGT and DM are small in Japanese patients. On the other hand, as glucose intolerance increases, insulin secretion decreases most remarkably both between NGT and IGT and between IGT and DM in Japanese patients. Decreasing insulin secretion and decreasing insulin sensitivity both occur in developing type 2 diabetes in Japanese patients, but decreased basal and early-phase insulin secretion had more pronounced contribution to glucose tolerance than the indices of insulin sensitivity. Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance.

Aging↗
PubMed1997

Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects.

OBJECTIVE: To investigate the relative contributions of insulin secretion and insulin resistance to the development of glucose intolerance in Japanese subjects. RESEARCH DESIGN AND METHODS: A cross-sectional study of 756 Japanese subjects (530 nonobese, 226 obese) was performed. A 75-g oral glucose tolerance test (OGTT) was given, and subjects were classified according to the World Health Organization (WHO) criteria (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes). Early-phase insulin secretion was assessed by the insulinogenic index (the ratio of the increment of insulin to that of plasma glucose [PG] 30 min after a glucose load [delta IRI0-30 min/delta PG0-30 min]). Total insulin secretion was assessed by mean immunoreactive insulin (IRI) during the OGTT, and insulin resistance was assessed by use of the homeostasis model [HOMA(R)]. RESULTS: Early-phase insulin secretion was significantly decreased in IGT, compared with patients with NGT, in both the nonobese and obese subjects (0.70 +/- 0.05 vs. 0.37 +/- 0.03, P < 0.01 and 1.36 +/- 0.19 vs. 0.73 +/- 0.08, P < 0.01, respectively). However, mean IRI and HOMA(R) in both nonobese and obese subjects with IGT and NGT were not statistically different. Subjects with diabetes showed a significant decline in early-phase and total insulin secretion and a significantly higher level of insulin resistance than did subjects with IGT. When the fasting glucose (FPG) exceeded 100 mg/dl, early-phase insulin decreased progressively. The graphed relationship between FPG and mean IRI did not show an inverted U-shape, and mean IRI decreased progressively when FPG exceeded 100-130 mg/dl. The pattern of changes in insulin secretion and insulin resistance associated with the progression of glucose intolerance was similar in both the nonobese and obese subjects. CONCLUSIONS: The worsening from NGT to IGT in Japanese subjects may be associated with a decrease in early-phase insulin secretion in nonobese as well as in obese subjects. Hyperinsulinemia in IGT is not common. We suggest that impaired early-phase insulin secretion may be the initial abnormality in the development of glucose intolerance in Japanese people. Insulin resistance may be a consequence of hyperglycemia and/or obesity.

Adult↗
PubMed2006

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects.

AIM: To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. METHODS: A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. RESULTS: Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. CONCLUSIONS: A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased.

Adolescent↗
PubMed2006

Sterol regulatory element-binding protein 1 mediates liver X receptor-beta-induced increases in insulin secretion and insulin messenger ribonucleic acid levels.

Liver X receptors (LXRalpha and LXRbeta) regulate glucose and lipid metabolism. Pancreatic beta-cells and INS-1E insulinoma cells express only the LXRbeta isoform. Activation of LXRbeta with the synthetic agonist T0901317 increased glucose-induced insulin secretion and insulin content, whereas deletion of the receptor in LXRbeta knockout mice severely blunted insulin secretion. Analysis of gene expression in LXR agonist-treated INS-1E cells and islets from LXRbeta-deficient mice revealed that LXRbeta positively regulated expression of ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding protein 1 (SREBP-1), insulin, PDX-1, glucokinase, and glucose transporter 2 (Glut2). Down-regulation of SREBP-1 expression with the specific small interfering RNA blocked basal and LXRbeta-induced expression of pancreatic duodenal homeobox 1 (PDX-1), insulin, and Glut2 genes. SREBP-1 small interfering RNA also prevented an increase in insulin secretion and insulin content induced by T0901317. Moreover, 5-(tetradecyloxy)-2-furoic acid, an inhibitor of the SREBP-1 target gene acetyl-coenzyme A carboxylase, blocked T0901317-induced stimulation of insulin secretion. In conclusion, activation of LXRbeta in pancreatic beta-cells increases insulin secretion and insulin mRNA expression via SREBP-1-regulated pathway. These data support the role of LXRbeta, SREBP-1, and cataplerosis/anaplerosis pathways in the control of insulin secretion in pancreatic beta-cells.

Alternative Splicing↗
PubMed2003

Promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human phosphatidylinositol 3-kinase are not associated with insulin secretion or insulin sensitivity in finnish subjects.

OBJECTIVE: Phosphatidylinositol (PI) 3-kinase activity is required for insulin-stimulated translocation of GLUT4 transporters and glucose uptake and utilization. Therefore, genes encoding the subunits of PI 3-kinase are promising candidate genes for insulin resistance and type 2 diabetes. We recently cloned the catalytic subunit p110beta gene of human PI 3-kinase and reported two nucleotide polymorphisms, -359T/C and -303A/G, in the promoter region of this gene. In this study, we determined the effects of these polymorphisms on insulin secretion and insulin sensitivity. RESEARCH DESIGN AND METHODS: We studied two separate groups of Finnish nondiabetic subjects. Insulin secretion was evaluated by intravenous glucose tolerance test and insulin sensitivity by hyperinsulinemic-euglycemic clamp. RESULTS: Our results showed that the -359T/C and -303A/G polymorphisms did not have a significant effect on fasting plasma insulin levels, insulin secretion, or insulin sensitivity. CONCLUSIONS: It is unlikely that the promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes in Finnish subjects.

Adult↗
PubMed2005

Intra- and inter-islet synchronization of metabolically driven insulin secretion.

Insulin secretion from pancreatic beta-cells is pulsatile with a period of 5-10 min and is believed to be responsible for plasma insulin oscillations with similar frequency. To observe an overall oscillatory insulin profile it is necessary that the insulin secretion from individual beta-cells is synchronized within islets, and that the population of islets is also synchronized. We have recently developed a model in which pulsatile insulin secretion is produced as a result of calcium-driven electrical oscillations in combination with oscillations in glycolysis. We use this model to investigate possible mechanisms for intra-islet and inter-islet synchronization. We show that electrical coupling is sufficient to synchronize both electrical bursting activity and metabolic oscillations. We also demonstrate that islets can synchronize by mutually entraining each other by their effects on a simple model "liver," which responds to the level of insulin secretion by adjusting the blood glucose concentration in an appropriate way. Since all islets are exposed to the blood, the distributed islet-liver system can synchronize the individual islet insulin oscillations. Thus, we demonstrate how intra-islet and inter-islet synchronization of insulin oscillations may be achieved.

Adenosine Diphosphate↗
PubMed1996

Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation.

An A-to-G transition in the mitochondrial tRNALeu(UUR) gene at base pair 3243 has been shown to be associated with the maternally transmitted clinical phenotype of NIDDM and sensorineural hearing loss in white and Japanese pedigrees. We have detected this mutation in 25 of 50 tested members of five white French pedigrees. Affected (mutation-positive) family members presented variable clinical features, ranging from normal glucose tolerance (NGT) to insulin-requiring diabetes. The present report describes the clinical phenotypes of affected members and detailed evaluations of insulin secretion and insulin sensitivity in seven mutation-positive individuals who have a range of glucose tolerance from normal (n = 3) to impaired (n = 1) to NIDDM (n = 3). Insulin secretion was evaluated during two experimental protocols: the first involved the measurement of insulin secretory responses during intravenous glucose tolerance test, hyperglycemic clamp, and intravenous injection of arginine. The second consisted of the administration of graded and oscillatory infusions of glucose and studies to define C-peptide kinetics. This protocol was aimed at assessing two sensitive measures of beta-cell dysfunction: the priming effect of glucose on the glucose-insulin secretion rate (ISR) dose-response curve and the ability of oscillatory glucose infusion to entrain insulin secretory oscillations. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Evaluation of insulin secretion demonstrated a large degree of between- and within-subject variability. However, all subjects, including those with NGT, demonstrated abnormal insulin secretion on at least one of the tests. In the four subjects with normal or impaired glucose tolerance, glucose failed to prime the ISR response, entrainment of ultradian insulin secretory oscillations was abnormal, or both defects were present. The response to arginine was always preserved, including in subjects with NIDDM. Insulin resistance was observed only in the subjects with overt diabetes. In conclusion, the pathophysiological mechanisms responsible for the development of NIDDM and insulin-requiring diabetes in this syndrome are complex and might include defects in insulin production, glucose toxicity, and insulin resistance. However, our data suggest that a defect of glucose-regulated insulin secretion is an early possible primary abnormality in carriers of the mutation. This defect might result from the progressive reduction of oxidative phosphorylation and implicate the glucose-sensing mechanism of beta-cells.

Adenine↗
PubMedDate not supplied

[The role of insulin secretion and insulin resistance in the clinical course of newly diagnosed diabetes mellitus in children].

BACKGROUND: The prevailing type of diabetes in Caucasian children and adolescents is type l. Insulin resistance resulting from decreased physical activity and obesity may account for the rising incidence of type l and type 2 diabetes mellitus in this group. AIM: To estimate the role of insulin secretion and insulin resistance in the clinical course of new onset type l diabetes mellitus in children and adolescents. MATERIALS AND METHODS: 58 patients aged 7.6-17.9 years, underwent investigations within the first 7 days after diabetes mellitus diagnosis. In 56 individuals type l and in 2 - type 2, was diagnosed. Insulin secretion was estimated by measurement of the serum C-peptide concentration in glucagon test while the Euglycemic-hyperinsulinemic clamp was performed to assess insulin resistance. HbA1c, glycemia and pH were examined. Body mass index (BMI) and the required daily dose of insulin (DDI) were calculated. RESULTS: In patients with diabetes C-peptide level was 0.03-1.5 pmol/ml. Index M ranged from 1.5 to 13.09 mg/kg/min. The hyperbolic relation was observed between C-peptide level and index M (r=0.62). There was a positive correlation between age at diabetes onset and C-peptide level (r=0.25) and negative with index M (r=-0.59). C-peptide level and index M correlated with body mass index (r=0.58; r=0.59; respectively). A relationship between glycemia and C-peptide level (r=-0.42) and index M (r=0.26) was found. Correlation between HbA1c and C-peptide level (r=-0,42; p=0.001) and index M (r=0.3) was observed. Dose of insulin correlated with C-peptide level (r=-0,2). CONCLUSIONS: In children with newly diagnosed diabetes mellitus a great variability of insulin secretion and insulin resistance was observed and a hyberbolic function between them. There was a relationship between insulin secretion and insulin resistance with age at onset and obesity. C-peptide level mainly determined HbA1c, glycaemia, pH and the needed dose of insulin.

Adolescent↗
PubMed1991

Comparative modulations of insulin secretion, pancreatic insulin content, and proinsulin mRNA in rats. Effects of 50% pancreatectomy and dexamethasone administration.

These studies compared measurements of in vivo insulin secretion, insulin stores, and insulin synthesis. Rats were studied at 24 wk of age, either 1 or 20 wk after a sham operation (Sham) or 50% pancreatectomy (Px), reducing beta-cell number. By 20 wk after surgery, an adaptation to pancreatectomy was apparent from results of serial glucose tolerance tests, done in a preliminary protocol. Some of the rats also received dexamethasone (ShamDex and PxDex, respectively), imposing insulin resistance. Insulin secretion was assessed with the acute insulin response to arginine under basal (AIRbas) and maximum glucose-potentiated (AIRmax) states. Pancreatic insulin was measured, and insulin synthesis was estimated by measurement of proinsulin mRNA. At 1 wk after surgery, there was no difference among Sham and Px rats in AIRbas, but in the Px rats, expected reductions of AIRmax, pancreatic insulin, and proinsulin mRNA were found. ShamDex rats had a markedly augmented AIRbas and increased AIRmax and proinsulin mRNA. However, pancreatic insulin was reduced both in ShamDex and PxDex rats. At 20 wk after surgery, the predicted adaptation to Px was substantiated by AIRmax and proinsulin mRNA in Px rats not different from those in Sham rats, but pancreatic insulin in the Px rats remained low. AIRbas and proinsulin mRNA were augmented in ShamDex and PxDex rats, but pancreatic insulin was again reduced, and in PxDex rats, low AIRmax and fed hyperglycemia were seen. Linear correlations of AIRbas and AIRmax with proinsulin mRNA were observed over a roughly fourfold range of secretion and synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2002

Effect of hormone replacement therapy on insulin secretion and insulin sensitivity in postmenopausal diabetic women.

The aim of the present study was to evaluate the effect of three different combinations of hormone replacement therapy (HRT) on insulin secretion, peripheral insulin sensitivity, serum lipid levels and parameters of oxidative stress. Seven type II diabetic women of mean age 55.4 +/- 4.7 years, who had been menopausal for an average of 5 years, were enrolled in the study. Phases of insulin secretion--first (FPIS) and second (SPIS)--and the area under the curve (AUC) for insulin secretion were studied during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was determined using the manual euglycemic-hyperinsulinemic clamp technique. Three different HRT combinations were applied consecutively for 3-month periods: estradiol valerate plus cyproterone acetate (Climen); transdermal 17 beta-estradiol (System TTS 50) plus dydrogesterone (Duphaston) 10 mg daily for 10 days a month; oral 17 beta-estradiol plus dydrogesterone (Femoston) for 14 days a month. A group of nine women with normal glucose tolerance (according to World Health Organization criteria during a 75-g oral glucose tolerance test (OGTT)), of mean age 50.1 +/- 8.2 years and mean body mass index 24.60 +/- 2.01 kg/m2, were also studied, and served as a control group. Insulin secretion improved significantly after Climen: FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 50% after Systen TTS 50 + Duphaston; fasting hyperinsulinemia was normalized and total antioxidant capacity of the serum (TAOCS) was significantly raised (p < 0.01). Femoston led to an increase in insulin sensitivity (by 23%) and in TAOCS (p < 0.05), while fasting hyperinsulinemia remained unchanged. HRT should be prescribed in type II diabetic postmenopausal women because of its favorable effect on existing pathophysiological defects. Cyproterone acetate should be preferred in cases with a predominant beta-cell insulin secretion defect, while dydrogesterone in combination with a transdermal estrogen should be recommended in cases with leading insulin resistance.

Administration, Cutaneous↗
PubMed1997

Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.

Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects. Using polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) on genomic DNA from 69 Danish NIDDM patients and 66 matched control subjects, we report the finding of three missense polymorphisms in otherwise conserved codons and three silent polymorphisms in the gene encoding Kir6.2: codon 23 (GAG/AAG), Glu-->Lys; codon 190 (GCT/GCC), Ala-->Ala; codon 267 (CTC/CTG), Leu-->Leu; codon 270 (CTG/GTG), Leu-->Val; codon 337 (ATC/GTC), Ile-->Val; codon 381 (AAG/AAA), Lys-->Lys. The codon 23 and codon 337 amino acid polymorphisms were always coupled. The allelic frequencies of the polymorphisms were similar in NIDDM patients and control subjects. The amino acid polymorphisms were not associated with altered insulin secretion after intravenous glucose or tolbutamide injections or with altered glucose effectiveness in a phenotype study of 346 young healthy subjects. However, carriers of the maximal load of amino acid variants, the compound homozygous codon 23/337 and heterozygous codon 270, had on average a 62% higher insulin sensitivity index (P = 0.006), compared with noncarriers. We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.

Adenosine Triphosphate↗
PubMed1996

Evidence for a circadian rhythm of insulin secretion.

Insulin secretion was studied in healthy volunteers at three different levels of glycemia. Plasma glucose was clamped at approximately 5, approximately 8.8 and approximately 12.6 mM for 68 h. Measured were serum insulin concentration and insulin secretion rates (ISR), the latter by deconvolution of plasma C-peptide concentration. Rhythmic patterns of ISR were identified (with a refined first-order Fourier transform) at all three glucose concentrations tested but were most clearly seen at 12.6 mM. ISR and serum insulin concentration changed in a circadian (approximately 24 h) rhythm, increasing from a nadir between midnight and 6 A.M. and reaching a peak between noon and 6 P.M. At 12.6 mM hyperglycemia, the amplitude of the insulin concentration cycles was greater than that of the ISR cycles (+/- 13.0 vs. +/- 8.7%) due to a decrease in insulin clearance (from 1.55 to 0.5 l/min, P < 0.01). Plasma melatonin levels (a marker of light-dark rhythmicity) changed in the opposite direction, i.e., they peaked when ISR bottomed and bottomed when ISR peaked. We concluded that normal human subjects have a circadian rhythm of insulin secretion, which becomes more apparent with rising ISR, and that circadian changes in ISR, rising during the day and falling during the night, may be one explanation for the well-established observation that glucose tolerance and insulin responses to glucose and meals are higher in the morning than at night.

Adult↗
PubMed2002

Age-dependent impact of zygosity and birth weight on insulin secretion and insulin action in twins.

AIMS/HYPOTHESIS: Study the influence of age, zygosity and birth weight on insulin action and insulin secretion in twins. METHODS: In vivo insulin action and insulin secretion were measured using the euglycaemic, hyperinsulinaemic clamp technique and intravenous glucose tolerance test, respectively. We examined 104 monozygotic (MZ) twins and 88 dizygotic (DZ) twins in two age groups (25-34 and 57-66 years). RESULTS: There were no differences in birth weight, body mass index, waist to hip ratio or lean body mass between monozygotic and dizygotic twins. Younger monozygotic twins had a slightly higher insulin-stimulated glucose uptake (M) than younger dizygotic twins. In contrast, elderly monozygotic twins had a lower insulin-stimulated glucose uptake value compared with elderly dizygotic twins. Elderly monozygotic twins had a reduced insulin secretion relative to insulin resistance compared to dizygotic twins during oral glucose tolerance test (OGTT). Birth weight per se was not associated with insulin secretion or action in the twins. However, correcting for the genetic influence on birth weight using intrapair differences among monozygotic twin pairs, low birth weight was associated with insulin resistance and low insulin secretion after both oral and intravenous glucose administration in elderly MZ twins. CONCLUSION/INTERPRETATION: Zygosity status has a major age (or time) dependent impact on in vivo insulin secretion and insulin action in twins independent of birth weight and adult antropometry. An additional non-genetic impact of low birth weight on insulin secretion and insulin action was found in elderly monozygotic twins. Ageing could play an important role by unmasking the influence of an adverse intrauterine environment on insulin resistance and low insulin secretion in twins.

Adult↗
PubMedDate not supplied

Diurnal variations in insulin secretion and insulin sensitivity in aged subjects.

Glucose tolerance tends to decrease in healthy aged subjects without family history of diabetes. Either reduced insulin secretion or insulin resistance may be responsible. Insulin secretion and insulin sensitivity were studied in 7 aged subjects (68-75 years) and 8 young controls (21-27 years). A 1-mg i.v. glucagon and a 5-U/m2 body area i.v. insulin test were run in each subject at 07(00) and at 19(00) on two different days to detect diurnal variations. An arginine test was also performed to evaluate pancreatic glucagon behavior. In the evening, young subjects presented a glucose tolerance impairment with significantly decreased plasma insulin levels, and a reduced hypoglycemic effect of exogenous insulin. Resistance to both endogenous and exogenous insulin in the aged was observed in the morning without significant morning/evening variations. Since the response to contra-insular hormones (GH in the insulin test, glucagon in the arginine test) was the same in both age groups, their role in the phenomenon could be ruled out. It is suggested that in the aged a stable reduction in number and/or a change in affinity of insulin receptors may occur. In addition, since aging is seen to be associated with the disappearance of diurnal variations in glucose tolerance and insulin secretion and sensitivity, and since a reduction in the receptor level of young healthy subjects in the evening has been reported by some authors, it is suggested that aged subjects may be less able to modulate the binding of insulin to its peripheral receptors in the course of the day.

Adult↗
PubMed1991

Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion.

Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women.

Adult↗
PubMed2003

Importance of obtaining independent measures of insulin secretion and insulin sensitivity during the same test: results with the Botnia clamp.

OBJECTIVE: To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (S(I)) during the same test; that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+) and without (FH-) a first-degree family history of diabetes. RESEARCH DESIGN AND METHODS: The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/kg glucose i.v. and insulin sensitivity (M-value) from a 2-h euglycemic clamp begun 60 min after the glucose bolus. The M-value obtained during the Botnia clamp was compared with M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance. Finally, the test was applied to subjects with and without a family history of type 2 diabetes. RESULTS: S(I) and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly with the M-value from a euglycemic clamp without prior glucose bolus (r = 0.953, P < 0.005). FH+ subjects showed decreased S(I) (P = 0.02), but similar FPIR, compared with FH- subjects. However, insulin secretion adjusted for the degree of insulin resistance was significantly impaired (P = 0.04). CONCLUSIONS: In conclusion, the Botnia clamp provides reliable and independent measures of S(I) and beta-cell function during the same test. As illustrated above, knowledge of the degree of S(I) is mandatory when presenting data on insulin secretion.

Diabetes Mellitus↗
PubMed2001

Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator--activated receptor-gamma2 gene.

The transcription of many genes involved in lipid metabolism is regulated by the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The Pro12Ala polymorphism in the PPAR-gamma2 gene has been associated with reduced transcriptional activity in vitro and increased insulin sensitivity in vivo. Although PPAR-gamma has been demonstrated in human beta-cells, it is unknown whether the Pro12Ala polymorphism plays a role in insulin secretion. Moreover, it is also unknown if and how the effect of free fatty acids (FFAs) on insulin secretion and insulin sensitivity is modulated by the presence of this polymorphism. We therefore performed hyperglycemic clamps (8 mmol/l, 140 min, 5 g arginine bolus at min 120) in 10 healthy subjects with the (X/Ala) polymorphism and in 10 subjects without the polymorphism (Pro/Pro) basally and after 5 h infusion of Intralipid plus heparin. FFA concentrations increased from 473 +/- 61 micromol/l to 1,732 +/- 163 micromol/l in the Pro/Pro and from 372 +/- 46 micromol/l to 1,630 +/- 96 micromol/l in the X/Ala group (P = 0.68). Basally, neither insulin sensitivity nor insulin secretion were significantly different between the two groups. During infusion of Intralipid, first-phase insulin secretion remained unchanged in both groups (P = 0.21). In the Pro/Pro group, second-phase insulin secretion remained unchanged (444 +/- 67 vs. 471 +/- 93 pmol/min) and the response to arginine increased from 5,007 +/- 41 to 6,072 +/- 732 pmol/min. In contrast, in the X/Ala group, there was a decrease of both second-phase insulin secretion (533 +/- 58 to 427 +/- 48 pmol/min, P = 0.02 vs. Pro/Pro) and in the response to arginine (from 7,518 +/- 1,306 to 6,458 +/- 1,040 pmol/min, P = 0.014 vs. Pro/Pro). The insulin sensitivity index decreased comparably in Pro/Pro and X/Ala (to 71 +/- 8 vs. 74 +/- 9% of basal, P = 0.8). In conclusion, these results provide evidence that the Pro12Ala polymorphism in the PPAR-gamma2 gene might be involved in a differential regulation of insulin secretion in response to increased FFAs in humans.

Alanine↗
PubMed2003

Lipid profile, insulin secretion, and insulin sensitivity in psoriasis.

BACKGROUND: Psoriasis has been associated with an abnormal plasma lipid metabolism and diabetes mellitus possibly related to alterations in insulin secretion and sensitivity. OBJECTIVE: We sought to identify lipid profile, insulin secretion, and insulin sensitivity in patients with psoriasis and healthy control patients. METHODS: A cross-sectional study was performed in 44 nonobese adults, 22 with psoriasis and 22 without. The psoriasis activity was evaluated by the psoriasis area and severity index. Insulin secretion was estimated using the homeostasis model analysis beta-cell function index. Insulin sensitivity was assessed with the insulin tolerance test. RESULTS: High-density lipoprotein cholesterol was significantly decreased in patients with psoriasis (P =.02). There were no significant differences in insulin secretion or sensitivity in patients with psoriasis compared with control patients. CONCLUSION: Patients with psoriasis had significantly decreased high-density lipoprotein cholesterol concentrations. There were no differences in insulin secretion or sensitivity compared with control patients.

Adolescent↗