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At least 217 records · Page 12Linked to original sources
PubMed2004

IRIS II Study: Sensitivity and specificity of intact proinsulin, adiponectin, and the proinsulin/adiponectin ratio as markers for insulin resistance.

OBJECTIVE: This study was performed to compare the specificity and sensitivity of intact proinsulin, adiponectin, and their ratio (proinsulin/adiponectin) in the prediction of insulin resistance as assessed by the homeostasis model assessment (HOMA) score (> or =2 = resistant). RESEARCH DESIGN AND METHODS: Using a cross-sectional approach, 500 orally treated patients with type 2 diabetes (272 women, 238 men; mean +/- SD age, 64.8 +/- 11.6 years; hemoglobin A1c, 7.0 +/- 1.5%; disease duration, 5.8 +/- 6.1 years) were investigated. Various cutoffs for body mass index-adjusted adiponectin and proinsulin/adiponectin were compared with the established cutoff value of 10 pmol/L for fasting proinsulin. RESULTS: Fasting proinsulin correlated more closely with the HOMA score (r = 0.560, P < 0.001) than fasting adiponectin (r = -0.204, P < 0.001) or proinsulin/adiponectin (r = 0.355, P < 0.001). For proinsulin, specificity and sensitivity for insulin resistance in correlation to the HOMA score results were 96% and 70%, respectively. At a comparable specificity level to proinsulin, adiponectin did not reach a comparable sensitivity (14%), while the proinsulin/adiponectin ratio almost reached the same sensitivity (65%). Overall, patients with elevated proinsulin had a higher prevalence of micro- and macrovascular disease [odds ratio 1.47 (adiponectin, 1.08; proinsulin/ adiponectin, 1.48) and 1.34 (adiponectin, 1.32; proinsulin/adiponectin, 1.27), respectively]. CONCLUSIONS: Elevation of fasting intact proinsulin seems to be the more specific marker for insulin resistance and increased cardiovascular risk than suppression of fasting adiponectin. Formation of the ratio does not lead to a further increase in the predictive value.

Adiponectin↗
PubMedDate not supplied

Improved beta cell function, with reduction in secretion of intact and 32/33 split proinsulin, after dietary intervention in subjects with type 2 diabetes mellitus.

Diet in Type 2 diabetes often reduces both hyperglycaemia and weight and both these factors may contribute to improvement in beta cell function. Sixty-nine subjects with newly diagnosed Type 2 diabetes had their glucose, insulin, intact and 32/33 split proinsulin measured at diagnosis, and after 16 (12-20) weeks of conventional diet. In the whole group following diet there was reduction in weight (p < 0.0001), Haemoglobin A1 (p < 0.0001), and fasting glucose (p < 0.0001). There was a fall in fasting intact proinsulin (p < 0.03), 32/33 split proinsulin (p < 0.0001), and the percentage of fasting proinsulin to total insulin-like molecules (p < 0.0001). Subjects were separated according to weight loss (group 1 < 0.5 kg, group 2 0.5-4 kg, group 3 > 4 kg). Only subjects in group 3 (mean weight loss 6.2 kg) had a fall in fasting insulin (p < 0.04). The fasting glucose achieved following diet was positively correlated with the initial fasting glucose (r = 0.7) and negatively correlated with the degree of insulin deficiency at diagnosis (with the initial 30 min insulin r = -0.62). The effect of diet on the final concentration of insulin, 32/33 split proinsulin and intact proinsulin was examined using multiple regression. The final insulin concentration was determined by the initial BMI and absolute weight loss, 32/33 split proinsulin concentration by the initial fasting glucose and absolute glucose fall, and intact proinsulin concentration by a combination of both weight loss and glucose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1994

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS: To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.

Acid-Base Equilibrium↗
PubMed1992

Dose-response characteristics of human proinsulin and insulin in non-insulin-dependent diabetic humans.

We compared the actions of human proinsulin and insulin on glucose turnover and on intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). Six diet-controlled weight-matched (25.4 +/- 1.0 kg/m2) NIDDM subjects underwent six separate isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6',6'-2H2]glucose. Each subject received three low-dose intravenous infusions of both insulin and proinsulin. Blood glucose was maintained at 6.7 +/- 0.3 mM during proinsulin and insulin infusion. Insulin (I) infusions gave steady-state levels of 0.12 +/- 0.001 (I1), 0.18 +/- 0.01 (I2), and 0.33 +/- 0.01 nM (I3). Steady-state proinsulin (P) levels were 2.5 +/- 0.1 (P1), 4.3 +/- 0.2 (P2), and 8.8 +/- 0.9 nM (P3). Hepatic glucose production was suppressed equally by proinsulin and insulin at all doses. The metabolic clearance rate of glucose was significantly increased during the insulin infusion compared with proinsulin. The use of [6',6'-2H2]glucose resulted in a mean underestimation of the glucose infusion rate of 10.0 +/- 4.0 and 6.0 +/- 2.5% during the two highest insulin and proinsulin doses, respectively. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids, blood glycerol, and beta-hydroxybutyrate levels (all P less than 0.05). Blood lactate levels were lower during the P1 (628 +/- 43 microM) and P2 (657 +/- 93 microM) infusions compared with I1 (776 +/- 60 microM) and I2 (878 +/- 44 microM; P less than 0.05, P less than 0.02), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1999

Proinsulin stimulates growth of small intestinal crypt-like cells acting via specific receptors.

The mechanisms that regulate cell turnover in the intestinal epithelium are incompletely understood. Here we tested the hypothesis that proinsulin, present in serum and pancreatic juice in picomolar concentrations, stimulates growth of the rat small intestinal crypt-like cell line IEC-6 under serum-free conditions. Proinsulin binding was assessed by competitive ligand binding studies. Proinsulin and insulin-like growth factor I (IGF-I) stimulated cell proliferation up to threefold above controls, with half-maximal action already in the picomolar range and with additive effects. In early confluent cell monolayers, proinsulin bound with higher affinity (IC50 1.3 +/- 0.05 nM) and capacity (87,200 +/- 2,500 receptors/cell) than IGF-I (4.0 +/- 0.6; 23,700 +/- 2,200, P < 0. 05). C-peptide competed with 10-fold lower affinity for binding of 125I-proinsulin but not for 125I-IGF-I or 125I-insulin, suggesting a specific binding epitope of the proinsulin molecule within or close to the C-peptide region. In contrast, insulin showed approximately 100-fold lower binding affinity and growth-promoting potency than proinsulin or IGF-I. We conclude that proinsulin stimulates growth of small intestinal crypt cells through specific binding and may play a physiological role in the regulation of intestinal epithelial cell proliferation.

Animals↗
PubMed2000

High proinsulin levels precede first-ever stroke in a nondiabetic population.

BACKGROUND AND PURPOSE: Diabetic subjects have a 3- to 6-fold increased risk for stroke compared with nondiabetic subjects, and hyperinsulinemia shows strong and consistent associations with a cluster of cardiovascular risk factors. Methods separating proinsulin from (true) insulin have demonstrated proinsulin to be more strongly associated with cardiovascular disease than insulin. The present study evaluates the associations between first-ever stroke, proinsulin, and insulin. METHODS: In this incident case-referent study of a nondiabetic population, 94 cases of first-ever stroke (59 men and 35 women) were individually age- and sex-matched to 178 referents. Blood sampling was collected before the stroke event. Proinsulin and insulin were measured with highly sensitive 2-site sandwich enzyme-linked immunosorbent assays. RESULTS: In the study population, high proinsulin concentration more than tripled the risk for first-ever stroke after adjustments for total cholesterol, systolic blood pressure, smoking, body mass index, and insulin, with an odds ratio of 3.4 (95% CI, 1.4 to 8.4). In women the risk was even more pronounced, with an odds ratio of 13.7 (95% CI, 1.3 to 146). Synergy was found between proinsulin and systolic blood pressure. In women, synergy was also found between proinsulin and diastolic blood pressure as well as between insulin and both blood pressures. CONCLUSIONS: High levels of proinsulin may predict later occurrence of first-ever stroke in a nondiabetic population.

Blood Pressure↗
PubMed1978

Characterization of proinsulin-insulin intermediates in human plasma.

This work addressed the problem of heterogeneity of immunoreactive insulin (IRI) in human plasma. Subjects with normal glucose tolerance were given 75g of an oral glucose solution, followed in 30 min by an intravenous infusion of 30g of arginine over 30 min. At the end of the infusion blood was withdrawn for analysis. IRI was extracted from plasma of individual subject by immunosorbent columns and was fractionated by gel filtration, disc gel electrophoresis and isoelectric focusing. Human IRI components were identified by molecular size, immunoreactivity with a human proinsulin antibody, sensitivity to trypsin, and by comparison of electrophoretic mobility and isoelectric point with porcine pancreatic products, after suitable correction for electric charge and molecular weight differences. The pattern of IRI heterogeneity was the same among six healthy subjects. Heterogeneity of proinsulin-size IRI in circulation was more marked than that of insulin-size material. Proinsulin and desdipeptide proinsulin were present in approximately equal amounts accompanied by minor amounts of split proinsulin and monodesamido-desdipeptide proinsulin. Insulin-size IRI contained over 80% insulin. Minor amounts of monodesamidoinsulin and diarginylinsulin were observed in some cases. The types of IRI components observed in plasma are evidence in support of a physiologic role of trypsin-and carboxypeptidase B-like enzymes in the conversion of proinsulin to insulin. Moreover, this study provides a base line for investigation of abnormalities in proinsulin-to-insulin conversion that may be associated with certain pathologic states.

Humans↗
PubMed1975

Carbohydrate metabolism in pregnancy: XIII. Relationships between plasma insulin and proinsulin during late pregnancy in normal and diabetic subjects.

To assess the effects of pregnancy on the relationships between plasma insulin and proinsulin, studies were performed during late gestation in women with normal carbohydrate metabolism or diabetes mellitus. Plasma was secured after overnight fast and 1, 2, and 3 hours following oral glucose (100 g). Samples were analyzed directly for total immunoreactive insulin (TIR) and for insulin and proinsulin following plasma fractionation by gel filtration. Fractionation disclosed that most of the normal gestational increase in basal and glucose-stimulated TIR can be ascribed to insulin rather than disproportionate increments in proinsulin-like components. Normal proinsulin/insulin relationships were also preserved in mild diabetics despite greater variability in their TIR response to glucose. Thus, mild carbohydrate intolerance during pregnancy is not attended by abnormalities in plasma proinsulin. In contrast basal proinsulin levels were elevated in 4 of 9 pregnant subjects with diabetes sufficiently severe to necessitate subsequent insulin therapy. Following glucose administration in the severe diabetics, the relative contribution from proinsulin to TIR was altered so that ratios of circulating proinsulin/insulin were increased at all levels of blood sugar. Postpartum tests of glucose tolerance in some of the normal and mildly diabetic subjects confirmed that pregnancy per se does not modify appreciably the relationships between plasma insulin and proinsulin although there may be some tendency for proinsulin to account for a smaller proportion of TIR.

Blood Glucose↗
PubMedDate not supplied

The relationship between BMI, plasma leptin, insulin and proinsulin before and after laparoscopic adjustable gastric banding.

BACKGROUND: Morbid obesity is associated with over-secretion of leptin and insulin, and predisposes to development of carbohydrate intolerance. In the current study, we explored the impact of BMI after laparoscopic adjustable gastric banding (LAGB) on leptin, insulin and proinsulin levels. METHODS: 23 obese patients (8 males, 15 females) were included in the study. Their mean age was 36+/-6 yrs (range 21-56 yrs). Blood samples were collected for measurement of plasma leptin, insulin and proinsulin before and 6 and 14 months after LAGB. RESULTS: Mean BMI before surgery was 46.04 +/- 4.44 kg/m2, with significant and equal reduction of 18% in each of the follow-up periods, with total BMI reduction of 33% (P <.0001). The levels of circulating leptin, insulin and proinsulin before intervention were 119.3 +/- 53.1 ng/ml, 159 +/- 13 pmol/l, and 36.36 +/- 23.06 pmol/l respectively. Despite an equal BMI reduction in the 2 follow-up periods, the most significant decrease in hormone levels was observed in the immediate postoperative period (54, 53, and 45%, respectively), when compared to the second follow-up period (15, 30, 10%, respectively). The highest total decline in hormone level of 70% was obtained with insulin, compared to 52% in leptin, and 50% in proinsulin. Despite the significant decrease in proinsulin and insulin levels, their ratio increased from 0.22, to 0.28 and 0.36 after LAGB. Unlike insulin and proinsulin, leptin levels strongly and persistently correlated with BMI during the study. CONCLUSION: Following LAGB, weight loss was associated with decreased levels of circulating leptin, insulin and proinsulin, most prominent in the first follow-up period. Unlike insulin and proinsulin, leptin showed the most significant and persistent correlation with BMI, suggesting that morbid obesity acts through different feedback hormonal mechanisms which are probably not regulated only by absolute weight loss. Longer follow-up and larger numbers of patients are needed to clarify long-term hormonal profile, as well as the beneficial lasting effects of such interventions.

Adult↗
PubMed1982

Effects of glucose on proinsulin messenger RNA in rats in vivo.

The purpose of these studies was to determine whether glucose, the principal regulator of insulin biosynthesis in mammals, controls synthesis through alterations in levels of proinsulin mRNA in whole animals. Rats were starved for 3 days and then either refed or injected with glucose or saline for 24 h. Glucose injection raised plasma glucose levels equivalent to levels seen with refeeding but provided less than 20% of caloric replacement. Pancreatic RNA was extracted and the relative concentration of proinsulin mRNA was determined by blot hybridization with a cloned rat proinsulin cDNA probe. In starved animals proinsulin mRNA levels were 15-20% that of fed controls. Glucose injection produced a specific three- to fourfold increase in proinsulin mRNA levels relative to total pancreatic RNA, within 24 h. The effect was measurable 2 h after glucose injection and appeared largely complete by 12 h. Actinomycin D blocked the glucose-induced increase in proinsulin mRNA. These studies demonstrate effects of changes of plasma glucose on levels of proinsulin mRNA. Their rapidity of onset and large magnitude are comparable to effects of glucose on rates of insulin biosynthesis in isolated islets and suggest that insulin biosynthesis is regulated at least in part by levels of proinsulin mRNA.

Animals↗
PubMed1989

Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity.

Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7-58 pM) vs. 3.8 pM (less than 1.2-28 pM) in control subjects (P less than .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60-237 pM) vs. 118 pM (71-175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a beta-cell more vulnerable to destruction, or it could reflect previous beta-cell damage that does not lead to IDDM.

Adolescent↗
PubMed1991

Relative hypersecretion of proinsulin in rat model of NIDDM.

The plasma ratio of proinsulin to insulin is raised in individuals with non-insulin-dependent diabetes mellitus (NIDDM). Increased secretion of proinsulin relative to insulin is thought to be the cause, although differential changes in clearance have not been ruled out. This study was conducted in a rat model of NIDDM, 90% pancreatectomized (Px) rats, to investigate the pathophysiology of this observation. Proinsulin storage and secretion were assessed with high-performance liquid chromatography separation of the insulins and the proinsulins, followed by quantification of the peaks by insulin radioimmunoassay. In Px rats, the relative proportion of proinsulin in pancreas extracts was twice that of control (sham-operated) rats (15.6 +/- 1.4 vs. 8.3 +/- 1.4%, P less than 0.01). Samples obtained from the portal vein during in vitro pancreas perfusion also had an elevated proinsulin fraction (Px, 10.3 +/- 3.0; sham, 3.0 +/- 0.6%; P less than 0.006). In summary, 90% Px rats share many pathophysiological features with NIDDM, including loss of normal proinsulin homeostasis. Our results suggest that chronic hyperglycemia causes an intrinsic change in beta-cells that is characterized by the increased storage and secretion of proinsulin.

Animals↗
PubMed1997

Elevated islet amyloid pancreatic polypeptide and proinsulin in lean gestational diabetes.

Recent research indicates that islet amyloid pancreatic polypeptide (IAPP) might have a regulatory effect on beta-cell insulin processing and secretion. To study such interaction in more detail, IAPP secretion and kinetics and the serum concentrations of proinsulin were assessed both before and after delivery in lean pregnant women with gestational diabetes mellitus (GDM patients) in comparison to those with normal glucose tolerance (NGT) and to nonpregnant healthy lean (control) and obese insulin-resistant women during oral glucose tolerance tests. Kinetic analysis of IAPP was performed with mathematical modeling, providing indirect estimates of its secretion and fractional clearance. Total insulin secretion per 180 min was elevated by 30% in GDM patients (35 +/- 3 pmol/l) versus control subjects (27 +/- 1 pmol/l) (P < 0.05), but increased even more (190-250%) in obese insulin-resistant women, compared with all other groups (68 +/- 7 pmol/l, P < 0.0005). Pregnancy induced a more marked fourfold increase in apparent total IAPP secretion rate (TIR) (GDM patients, 172 +/- 31 pmol x 1(-1) x 3 h(-1); NGT subjects, 166 +/- 31 pmol x 1(-1) x 3 h(-1); control subjects, 40 +/- 1 pmol 1(-1) x 3 h(-1)) and a twofold rise in its fractional clearance versus control subjects (P < 0.01), whereas in GDM patients a 30% increase of IAPP secretion and a decreased clearance was found, compared with obese insulin-resistant women (TIR, 112 +/- 14 pmol x 1(-1) x 3 h(-1)). The increase in IAPP secretion in both pregnant groups was much higher than that of the insulin groups, resulting in a marked change of the IAPP-insulin cosecretion factor when compared with lean or obese nonpregnant women (P < 0.0005). Associated serum proinsulin and the postprandial (total divided by 180 min) proinsulin-to-insulin ratio were greater in GDM patients versus NGT and control subjects (0.11 +/- 0.01 vs. 0.07 +/- 0.01 and 0.08 +/- 0.01 pmol/l, P < 0.05), while the fasting proinsulin-to-insulin ratio was only increased in GDM patients versus control subjects (0.22 +/- 0.03 vs. 0.13 +/- 0.01 pmol/l, P < 0.05). After delivery, total IAPP secretion (52.4 +/- 1.5 pmol/l) was completely normalized in the GDM group, as were the clearance rate and the IAPP-insulin cosecretion factor. Similarly, serum proinsulin concentrations returned to normal, whereas proinsulin-to-insulin ratios remained elevated. In conclusion, IAPP hypersecretion is characteristic for pregnancy and might partially decrease hyperinsulinemia in pregnancy by inhibiting insulin secretion. Increased proinsulin concentrations and a raised proinsulin-to-insulin ratio, which did not abate following delivery, are specific to GDM and might thus serve as its marker and potentially even identify subjects at high risk for the development of NIDDM.

Adult↗
PubMed2001

Glycerol-stimulated proinsulin biosynthesis in isolated pancreatic rat islets via adenoviral-induced expression of glycerol kinase is mediated via mitochondrial metabolism.

In this study, we examined whether adenoviral-mediated glycerol kinase (AdV-CMV-GlyK) expression in isolated rat pancreatic islets could introduce glycerol-induced proinsulin biosynthesis. In AdV-CMV-GlyK-infected islets, specific glycerol-induced proinsulin biosynthesis translation and insulin secretion were observed in parallel from the same islets. The threshold concentration of glycerol required to stimulate proinsulin biosynthesis was lower (0.25-0.5 mmol/l) than that for insulin secretion (1.0-1.5 mmol/l), reminiscent of threshold differences for glucose-stimulated proinsulin biosynthesis versus insulin secretion. The dose-dependent glycerol-induced proinsulin biosynthesis correlated with the rate of glycerol oxidation in AdV-CMV-GlyK-infected islets, indicating that glycerol metabolism was required for the response. However, glycerol did not significantly increase lactate output from AdV-CMV-GlyK-infected islets, but the dihydroxyacetone phosphate (DHAP) to alpha-glycerophosphate (alpha-GP) ratio significantly increased in AdV-CMV-GlyK-infected islets incubated at 2 mmol/l glycerol compared with that at a basal level of 2.8 mmol/l glucose (P < or = 0.05). The DHAP:alpha-GP ratio was unaffected in AdV-CMV-GlyK-infected islets incubated at 2 mmol/l glycerol in the added presence of alpha-cyanohydroxycinnaminic acid (alpha-CHC), an inhibitor of the plasma membrane and mitochondrial lactate/pyruvate transporter. However, alpha-CHC inhibited glycerol-induced proinsulin biosynthesis and insulin secretion in AdV-CMV-GlyK-infected islets (>75%; P = 0.05), similarly to glucose-induced proinsulin biosynthesis and insulin secretion in AdV-CMV-GlyK-infected and control islets. These data indicated that in AdV-CMV-GlyK-infected islets, the importance of mitochondrial metabolism of glycerol was required to generate stimulus-response coupling signals to induce proinsulin biosynthesis and insulin secretion.

Adenoviridae↗
PubMed1997

The relationship of concentrations of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. A study of two ethnic groups.

OBJECTIVE: To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: Fasting concentrations of proinsulin, des-31,32-proinsulin, and insulin, and of insulin 2 h after a 75-g glucose load, were measured in 1,034 nondiabetic europid subjects and 257 south Asian subjects and related to prevalent coronary heart disease (Minnesota-coded electrocardiographic criteria or ischemic chest pain). In 137 south Asian subjects, the fasting concentrations were related to incident coronary heart disease over a 6.5-year follow-up. RESULTS: The standardized odds ratios for prevalent coronary heart disease were as follows: fasting insulin, 1.29 (1.11-1.49), P = 0.0006; 2-h insulin, 1.25 (1.08-1.45), P = 0.003; proinsulin, 1.23 (0.99-1.53), P = 0.058; and des-31,32-proinsulin, 1.32 (1.03-1.69), P = 0.026. The odds ratios were similar in the two ethnic groups. These relationships became insignificant when controlling for age, sex, and BMI. The standardized odds ratios for incident coronary heart disease were as follows: fasting insulin, 0.99 (0.63-1.55), P = 0.97; proinsulin, 1.13 (0.72-1.78), P = 0.59; and des-31,32-proinsulin, 1.00 (0.61-1.63), P = 1.00. CONCLUSIONS: We have found similar relationships between concentrations of proinsulin-like molecules and prevalent coronary heart disease, as are observed for insulin in these nondiabetic subjects, although these molecules comprise only approximately 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.

Adolescent↗
PubMed1999

LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study.

OBJECTIVE: LDL particles are heterogeneous in terms of size and density; small dense LDL particles are considered more atherogenic than larger LDL particles. The aim of this study was to investigate the interrelationships among LDL size, insulin, proinsulin (intact and split), and insulin sensitivity in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detectable cross-reactivity with insulin, and LDL size was determined by gradient-gel electrophoresis. RESULTS: In univariate analyses, LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin-to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0.0001). In a multivariate regression model (adjusted for age, BMI, ethnicity, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.0001), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantly inversely related to proinsulin in men (P = 0.005 and P = 0.04 after further adjustment for the glucose tolerance status), but not in women (P > 0.15). CONCLUSIONS: We found an inverse relation of proinsulin to LDL particle size in a large tri-ethnic population with varying degrees of glucose tolerance. This relation was independent of age, BMI, and triglyceride and HDL cholesterol concentrations, and was more pronounced in men than in women.

Arteriosclerosis↗
PubMed2005

Significant association of insulin and proinsulin with clustering of cardiovascular risk factors.

AIM: To investigate the association between true insulin and proinsulin and clustering of cardiovascular risk factors. METHODS: Based on the random stratified sampling principles, 1196 Chinese people (533 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Biotin-avidin based double monoclonal antibody ELISA method was used to detect the true insulin and proinsulin, and a risk factor score was set to evaluate individuals according to the number of risk factors. RESULTS: The median (quartile range) of true insulin and proinsulin was 4.91 mIu/L (3.01-7.09 mIu/L) and 3.49 pmol/L (2.14-5.68 pmol/L) respectively, and the true insulin level of female subjects was significantly higher than that of male subjects (P = 0.000), but the level of proinsulin displayed no significant difference between males and females (P = 0.566). The results of covariate ANOVA after age and sex were controlled showed that subjects with any of the risk factors had a significantly higher true insulin level (P = 0.002 for hypercholesterolemia, P = 0.021 for high low-density lipoprotein cholesterol, P = 0.003 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) and proinsulin level (P = 0.001 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) than those with no risk factors. Furthermore, subjects with higher risk factor scores had a higher true insulin and proinsulin level than those with lower risk factor scores (P = 0.000). The multiple linear regression models showed that true insulin and proinsulin were significantly related to cardiovascular risk factor scores respectively (P = 0.000). CONCLUSION: True insulin and proinsulin are significantly associated with the clustering of cardiovascular risk factors.

Adult↗
PubMed1992

[A method for determination of proinsulin levels in serum using both insolubilized anti-insulin antibody and anti-C-peptide antibody].

A method is described for determination of proinsulin levels in serum. The principle of the assay is that proinsulin reacts with both anti-insulin and anti-C-peptide antibodies. The assay procedure is as follows; Anti-insulin antibody fixed to bacterial cell wall and insolubilized is incubated with test serum to form a complex of proinsulin-anti-insulin antibody (solid phase), followed by washing twice with buffer to eliminate free C-peptide. Then, glycin-HCl buffer is added to dissociate the bound proinsulin. After centrifugation, the supernatant is neutralized with NaOH and proinsulin in it is measured using RIA kit for CPR assay. The assay is simple, sensitive and reproducible. Neither insulin nor C-peptide contained in test serum influences the proinsulin levels determined by this assay. The mean +/- S.D. of the fasting serum proinsulin levels of healthy donors was 7.0 +/- 2.6 PM/l. A patient with insulinoma showed extremely high serum proinsulin level, which decreased to the normal range after extirpation of insulinoma.

Antibodies↗