Higher Insulin Response Research Articles

Effects of a meal rich in medium-chain saturated fat on postprandial lipemia in relatives of type 2 diabetics

ObjectivePatients with type 2 diabetes and their relatives (REL) have increased risk for cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), which is influenced by diet, is an independent risk factor for CVD. Little is known about the effects of medium-chain saturated fatty acids (medium-chain SFA) on PPL and gene expression in REL. The objective of this study was to test the hypothesis that medium-chain SFA cause larger PPL response in REL compared with controls (CON) and have a differential effect on circulating incretins and ghrelin and gene expression in muscle and adipose tissue in REL and CON. MethodsSeventeen REL and 17 CON received a fat-rich meal (79 energy percent from fat) based on medium-chain SFA (coconut oil). Plasma concentrations of triglycerides (TG), free-fatty acids, insulin, glucose, glucagon-like peptide-1, glucose-dependent insulintropic peptide, and ghrelin were measured before and during 240 min postprandially. Muscle and adipose tissue biopsies were taken at baseline and after the test meal. ResultsAfter the test meal, REL had a higher plasma TG response (P = 0.002) and a tendency toward higher insulin response (P = 0.100). A number of genes were upregulated in response to the meal rich in medium-chain SFA in CON, but not in REL. ConclusionA meal high in medium-chain SFA resulted in larger PPL response in REL than in CON. It remains to be clarified whether this can be reproduced by a pure medium-chain fat (MCT) load. The meal exerted a differential effect on gene expression in muscle, but not adipose tissue, of REL compared with CON.

Berries Reduce Postprandial Insulin Responses to Wheat and Rye Breads in Healthy Women

Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13–20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry purée or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries.

Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women

Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.

Hiperglucemia en ayunas y polimorfismo en el promotor de la glucoquinasa (rs1799884)

Glucokinase is one of the most important regulators of fasting glucose levels. There are several mutations in the glucokinase gene ( GCK) which are linked with monogenic diabetes. Recently, a polymorphism in its promoter has been described, which is associated with impaired fasting glucose levels. We present a 7 years and 7 months old boy with overweight and a familial background of diabetes in two previous generations. In the oral glucose tolerance test, he had impaired fasting glucose levels and after two hours, with a high insulin response. Laboratory abnormalities improved after weight loss, but he maintains a slight fasting hyperglycaemia. The molecular study of the most common monogenic diabetes forms, MODY subtypes 1, 2, and 3, was negative. The allelic variant G/A was however detected at the GCK promoter polymorphism rs1799884.

Influence of the glycemic load (GL) on subjective and objective measures of sleep quality in insomnia

Evidence in healthy sleepers suggests the glycemic index (GI) can mediate changes in sleep onset latency, given the availability of tryptophan to the brain (i.e. TRP/LNAA ratio) is increased after high GI carbohydrate-only food. However, these meals have limited clinical application given the high glycemic load (GL) and insulin responses. Therefore, we investigated the efficacy of a mixed macronutrient high GI (MHGI) compared to an isoenergetic (∼1915 kJ) low GI (MLGI) meal taken three hours prior to habitual bedtime to improve sleep quality in participants meeting research diagnostic criteria for insomnia. Four men and four women (n=8) were randomized to the MHGI or MLGI meal for two consecutive nights. Blood samples were taken prior to the meal, and 60, 120, 180 min after eating. Subjective (sleep diary) and objective (polysomnography, PSG) sleep was also measured each night. The individual 10cm visual analogue scales indicate that meal palatability was identical for both meals; which were of good taste (average 7.8cm); meal satiety was maintained until bedtime after the MHGI meal (>5cm), whereas after the MLGI meal satiety ratings in men were low (<5cm); and the average meal energetic load (kJ/kg) was greater for women (33.0 ± 4.1) than men (25.4 ± 3.8; p<0.05). Postprandial measures indicate glucose was larger after the MHGI meal but there was no difference in insulin response; the peak percentage rise in plasma TRP/LNAA from baseline after the MHGI meal (17%) was substantially but only marginally different than the MLGI (8%) meal (p = 0.12); postprandial serotonin was unaltered. The participant group self-reported (5pt Likert scale) feeling more rested after the MHGI (2.8) compared to the MLGI meal (2.3; p<0.05); also ratings were higher in women (3.0) than in men (2.6; p<0.05). There were no differences in PSG sleep variables. This study demonstrates symptoms of insomnia are improved, especially in women, after a high GI mixed macronutrient meal. Given the present data, we suggest the possibility for a physiological threshold within the postprandial plasma TRP/LNAA response that must be surpassed in order to promote measurable changes to serotonin and PSG sleep. Further studies should evaluate the potential long-term risks and benefits of habitual mixed macronutrient high GI meals to improve sleep.

Energy expenditure, urea kinetics, and body weight gain within a segregating resource family population

Beef and dairy cattle represent divergent metabolic types that disseminate nutrients into either meat or milk and differ in nutrient accretion. To investigate nutrient flow and turnover in an animal model combining beef and dairy cattle, a crossbred experiment has been started. An F2 resource population was generated from Charolais (beef breed) sires and German Holstein (dairy breed) cows as P0 founders by consistent use of embryo transfer to establish the F1 and F2 generations, which accordingly comprised half- and full-sib offspring. In 64 bulls of 5F2 families, dry matter intake and growth performance were measured monthly, and carcass composition was determined after slaughtering at 18 mo of age. Energy expenditure and urea kinetics were investigated via stable isotope tracer techniques using an intravenous single bolus dose of sodium [13C]bicarbonate [2.5μmol/kg of body weight (BW), 99 atom% 13C] at 8 and 18 mo of age and of [15N]urea (0.28 mg/kg of BW, 99 atom% 15N) at 8 mo of age, respectively. Insulin responses were measured via glucose tolerances tests at the age of 8 mo. The results revealed significant differences between families for growth performance, energy expenditure, and urea kinetics. In summary, low energy expenditure was associated with high average body mass gain and high insulin response. A greater urea loss was associated with reduced muscle protein in carcass. In addition, corresponding half-sib and full-sib sisters from bulls with highest growth rate indicated highest milk production. In conclusion, we have demonstrated that differences in energy expenditure and urea kinetics result in differences in average daily gain and carcass traits and vice versa in F2 crossbred bulls with common beef and dairy genetic backgrounds.

Dietary glycemic index, glycemic load, insulin index, fiber and whole-grain intake in relation to risk of prostate cancer.

Insulin may play a role in prostate cancer tumorigenesis. Postprandial blood glucose and insulin responses of foods depend importantly on the carbohydrate quality and quantity, represented by glycemic index (GI), glycemic load (GL), fiber and whole-grain content, but are also influenced by intake of protein and other characteristics. The recently developed insulin index (II) quantifies the postprandial insulin secretion, also taking into account these additional characteristics. We investigated the association between dietary GI, GL, II, fiber, and whole grains and risk of total prostate cancer (n=5,112) and subgroups of prostate cancer as defined by stage or grade in 49,934 male participants of the Health Professionals Follow-up Study. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. Dietary GI, GL, II, or fiber was not associated with risk of total or subgroups of prostate cancer. We observed a positive association between dietary intake of whole grains and total prostate cancer (HR highest versus lowest quintile 1.13, 95% CI 1.03-1.24), which was attenuated after restriction to PSA-screened participants (HR 1.03, 95% CI 0.91-1.17). These results suggest that long-term exposure to a diet with a high insulin response does not affect prostate cancer incidence.

Postprandial hyperglycemia and insulin response are affected by sea buckthorn (Hippophaë rhamnoides ssp. turkestanica) berry and its ethanol-soluble metabolites

Repeated postprandial hyperglycemia and subsequent mild, late hypoglycemia as well as high postprandial insulin response lead to metabolic events that may eventually develop into type 2 diabetes. The aim of this study was to assess how sea buckthorn berries as well as two sea buckthorn extraction residues modulate the postprandial metabolism after a high-glucose meal. Ten healthy normal-weight male volunteers consumed four study breakfasts, one control (A) and three sea buckthorn meals on four distinct study days. All the meals contained yoghurt and glucose (50 g). The sea buckthorn ingredients used were dried and crushed whole berries (meal B1), supercritical fluid (SF)-carbon dioxide (CO(2))-extracted oil-free berries (meal B2) or ethanol-extracted SF-CO(2)-extraction residue (meal B3). Blood samples for glucose, insulin and tumor necrosis factor-α analyses were collected before and during the 6-h study period. Meal B1 suppressed the postprandial peak insulin response when compared with meal A (Δconcentration of 30-min peak value--21.8 mU/l, P=0.039), and stabilized postprandial hyperglycemia and subsequent hypoglycemia (Δconcentration of 30-min peak value--120-min value -30.4 mU/l, P=0.036). Furthermore, meal B2 resulted in a more stable insulin response than the control meal (Δconcentration of 30-min peak value--120-min value -25.9 mU/l, P=0.037). Removal of the CO(2)-soluble oil component from the berries did not show a significant change in the studied postprandial effects of the berries. The EtOH soluble components, again showed advantageous properties in both insulin and glucose responses.

Protein and starch concentrates of air-classified field pea and zero-tannin faba bean for weaned pigs.

Air-classified pulse (non-oilseed legume) protein and starch may replace specialty protein and starch feedstuffs in diets for weaned pigs. In Exp. 1, three specialty protein sources (5% soy protein concentrate, 5% corn gluten meal, and 5% menhaden meal in the control diet) were replaced with 16% zero-tannin hulled or dehulled faba bean, or 17.5% field pea protein concentrate. In total, 192 group-housed pigs (2 gilts and 2 barrows per pen; BW = 7.5 +/- 1.4 kg) were fed wheat-based diets (3.60 Mcal/kg of DE and 3.3 g of standardized ileal digestible Lys/Mcal DE) over 28 d for 12 pen observations per each of 4 diets. Overall, protein source did not affect ADFI, ADG, or G:F. Apparent total tract digestibility (ATTD) of DM, GE, and P was greater (P < 0.05) for dehulled faba bean and field pea protein concentrate diets than the diet with 3 specialty protein sources. In Exp. 2, faba bean and field pea starch concentrates were compared with corn, wheat, tapioca, and potato starch as dietary energy sources. In total, 36 individually housed barrows (BW = 8.0 +/- 1.5 kg) were fed 1 of 6 diets for 15 d. Feces and urine were collected from d 8 to 14, and jugular blood was sampled after overnight fast and refeeding on d 15. Starch source did not affect N retention as a percentage of N intake. For d 0 to 14, ADFI of pigs fed field pea starch was greater (P < 0.05) than pigs fed corn, wheat, potato, and faba bean starch. Pigs fed tapioca, field pea, wheat, or corn starch grew faster (P < 0.05) than those fed faba bean or potato starch. For d 0 to 14, pigs fed corn or wheat starch had a 0.1 greater (P < 0.05) G:F than pigs fed faba bean, field pea, or potato starch. The ATTD of DM, GE, CP, and starch and the DE value of potato starch were much less (P < 0.05) than those of other starch diets. Postprandial plasma glucose was 4.9, 6.3, and 9 mmol/L greater (P < 0.05) for pigs fed tapioca than for pigs fed faba bean, wheat, and potato starch, respectively. However, postprandial plasma insulin tended to be 844 and 577 pmol/L greater (P < 0.10) for pigs fed faba bean and corn starch, respectively, than for pigs fed potato starch. The high insulin response of pigs fed faba starch could not be explained. In conclusion, air-classified pulse protein concentrates can replace specialty protein feedstuffs in diets for weaned pigs. Feeding air-classified pulse starch concentrates to starter pigs achieved a similar N retention as a percentage of N intake. The factors responsible for the reduced ADFI associated with feeding faba bean starch remain unclear.

Glycemic and Insulinemic Responses Are Affected by Age of Horse and Method of Feed Processing

The objective of this study was to examine age-related differences in glycemic and insulinemic responses of horses that were fed various feedstuffs, with particular attention to method of feed processing. A 16 × 16 Latin square design was used with eight 2-year-olds and eight mature Arabians. Horses were maintained on a roughage diet and were subjected to a glycemic response test once weekly. A control treatment consisted of an oral dextrose drench (0.25 g dextrose/kg of BW). Ten treatments consisted of variously processed feed ingredients fed at the rate of 1.5 g/kg of BW. Five other treatments were commercial feeds of a proprietary nature and are not reported. Fasting blood samples were taken once a week for 16 weeks. Thirty minutes later, another baseline sample was taken and horses were administered their respective treatment. Further blood samples were taken every 30 minutes through four hours. Samples were analyzed for glucose and insulin concentrations. Differences in glucose response between 2-year-olds and mature horses were minimal. However, mature horses had a higher insulin response ( P < .01) suggesting young horses had greater insulin sensitivity. Additionally, differences ( P < .05) existed between treatments with pelleted steam-processed corn having the highest glycemic response and cracked corn the lowest. Results from this study confirm that mature horses have reduced insulin sensitivity and that both glycemic and insulinemic responses are altered with feed processing techniques. Thermal processing produces the greatest response; however, a low glycemic response may not be desirable if starch escapes into the hindgut.

Abstract 2823: Dietary glycemic index, glycemic load and insulin index, in relation to risk of prostate cancer

Abstract Background: The insulin and insulin-like growth factor (IGF) axis has been shown to play a role in prostate cancer tumorigenesis. Circulating IGF-1 and fasting insulin as well as insulin resistance have been associated with increased risk of total or advanced prostate cancer in some epidemiological studies. Through alterations by diet the insulin and IGF axis may be potentially modifiable. The dietary insulin response depends largely but not entirely on the quality and quantity of dietary carbohydrates. The glycemic index (GI) is a measure of the propensity of carbohydrate containing foods to raise blood glucose levels postprandially. The more recently developed food insulin index is a comparable measure which is based on the diet's effect on insulin secretion, also taking into account foods with low or no carbohydrate content. We hypothesized that high dietary glycemic index, glycemic load (GL) and insulin index (II) are associated with increased risk of prostate cancer. Material and Methods: We followed 47,779 Health Professionals Follow-up Study participants between 1986 and 2006 for prostate cancer incidence. Dietary intake was assessed by food frequency questionnaire (FFQ) in 1986 and updated every 4 years. Dietary GL was calculated by multiplying GI by the carbohydrate content and consumption frequency of each FFQ item and then summing over all the items. Values for the food insulin index of the FFQ items were provided by the University of Sydney, Australia. The dietary II was calculated as a function of food insulin index, energy content and consumption frequency of all FFQ items. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results: Between 1986 and 2006, we confirmed 5,112 prostate cancer cases, including 860 advanced/fatal (regionally invasive or metastatic disease at diagnosis, or metastases or death from prostate cancer during follow-up) cases. Dietary GI, GL and II were not associated with risk of total or advanced prostate cancer. For total prostate cancer, the multivariate adjusted HRs comparing the highest versus lowest quintile were 1.01 (CI 0.92-1.12, p-trend=0.26) for GI, 1.07 (CI 0.97-1.19, p-trend=0.19) for GL and 1.05 (CI 0.94-1.17, p-trend=0.15) for II. For advanced prostate cancer, the HRs were 1.05 (CI 0.75-1.47, p-trend=0.76) for GI, 0.99 (CI 0.70-1.40, p-trend=0.64) for GL, and 0.99 (CI 0.68-1.44, p-trend=0.92) for II. Results did not change substantially when the cohort was restricted to men with PSA screening. Stratification by BMI, diabetes and age at diagnosis, or by tumor grade, did not suggest any heterogeneity (all p-values for interaction were &amp;gt;0.11). Conclusion: These results suggest that long-term exposure to a diet with a high insulin response as reflected by high dietary glycemic index, glycemic load and insulin index does not affect prostate cancer incidence or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2823.

Reactive Hypoglycemia Associated with Transient Hyperthyroidism in the Background of the Prediabetic Stage

A 70-year-old woman suffered from hypoglycemic symptoms three or four hours after glucose intake for three months. At this time, the patient felt she had perspired more than in previous years. A diffuse elastic goiter without tenderness was palpable. Transient hyperthyroid state with little uptake by 123I-thyroid scintigram was shown and diagnosed as silent thyroiditis. Oral glucose ingestion test (OGTT) showed normal glucose response but high insulin response and hypoglycemia occurred at 240 minutes. We diagnosed reactive hypoglycemia for glucose intake. The frequency of hypoglycemia reduced after the glucose intake decrease. Hypoglycemia did not occur after glucose intake in the euthyroid state. Then OGTT showed a borderline pattern and delayed hyperinsulinemic response. Reactive hypoglycemia may have been the result of transient hyperthyroid state in the background of the pre-diabetic stage.

Effect of Long-term Administration of Insulin and Glibenclamide on Pancreatic A and B Cell Function

To investigate the effects of insulin and sulfonylurea drug administration on islet A and B-cell functions, insulin and glucagon response was studied in normal rats treated with insulin (4 U/day subcutaneously) or glibenclamide (0.03 mg/kg intraperitoneally) for 8 weeks. In intravenous glucose tolerance test (0.5 g/kg), lower insulin response and impaired glucose tolerance were observed in insulin-treated rats and higher insulin response and impaired glucose tolerance were observed in glibenclamide-treated rats. In perfused pancreas, insulin response to glucose and arginine was significantly lower in insulin-treated rats and that was significantly higher in glibenclamide-treated rats. Glucagon response was not altered by insulin or glibenclamide treatment. These results suggest that hyperinsulinisation and glibenclamide administration strongly influence pancreatic B-cell function but not influence pancreatic A-cell function.

Association between serum insulin and bone mass in overweight/obese postmenopausal women

It is well established that both fat and muscle masses are positively related to bone mass. Other than just providing a mechanical stimulus, the influence of fat/muscle might be related to their ability to modulate bone cells via other hormonal influences. Higher than necessary food consumption (eventually leading to higher weight/fat) results in continuous higher insulin response. It has been shown in clinical and animal studies that circulating insulin is positively related to BMD/BMC and although individuals with insulin resistance develop other abnormalities, their bone mass is typically higher. This is attributed to the role of insulin in mediating other hormones, including calcitonin, PTH and androgens. Our objective was to evaluate the relationship between insulin and BMD/BMC of various skeletal sites with regard to the adipocity level (expressed as body mass index-BMI kg/m) in overweight/obese postmenopausal women. Participants included 110 Caucasian healthy women aged (mean±SD) 55.9±4.1 yr and BMI of 31.9±4.8 kg/m, without diabetes, insulin resistance, or other diseases/medications known to affect bone. Weight/height was measured in indoor clothing and used to calculate BMI; BMD/BMC was measured by iDXA; fasting serum insulin was measured by ELISA (Alpco Diagnostics, Salem, NH). Women were stratified into 4 categories based on their BMI: overweight (BMI=25–29.9) obese I (BMI=30– 34.9), obese II (BMI=35–39.9), and obese III (BMI>40). ANOVA results showed significantly higher (p<0.05) insulin levels in heavier women (6.3±4.0; 9.7±8.1; 12.4±7.5; and 16.0±18.9 μIU/ml, respectively, based on the above stratification). The heavier women also had a higher BMD/BMC in various skeletal sites, although statistical significance was not always reached. Regression models adjusted for BMI and age, showed positive significant (p<0.05) relationship between BMD/BMC of hip, forearm and spine and insulin levels. Our results show that circulating insulin is positively associated with BMD/BMC of various skeletal sites independently of adiposity/BMI in healthy overweight women. Funded: USDA/CSREES/NRI #2004-05287. Conflict of interest: None declared.

Noncompartmental pharmacokinetics analysis of glucose‐stimulated insulin response in African–American and Caucasian youths

The objective of this study was to examine the differences in glucose and insulin responses between African-American and Caucasian youths and to determine the associations of between-group differences with sex, body mass index (BMI) and pubertal status using a noncompartmental pharmacokinetic approach. Sixteen African-American and 22 Caucasian healthy adolescents were tested using the frequently sampled intravenous glucose tolerance test. Longitudinal t-tests across each observation revealed that (1) African-American youths have higher insulin concentrations between 4 to 19 min; (2) insulin levels remained similar as subjects were grouped according to sex and pubertal status; (3) for glucose, the only difference was found as it approached steady-state basal level (>100 min) between groups with different BMIs. Linear regression showed that insulin concentrations between 4 to 19 min are associated with BMI in Caucasians. African-American youths were found to have higher insulin responses after glucose stimulation and the insulin concentrations were more related to BMI in Caucasians compared with African-Americans. BMI also has a significant effect on the glucose steady state basal level. The acute insulin response to glucose (AIR(g)) extended to 20 min resulted in a more significant racial difference (p<0.0006) compared with the calculation done over 10 min suggested in the past (p<0.001).

Molecular Analysis of db Gene-related Pancreatic .BETA. Cell Dysfunction; Evidence for a Compensatory Mechanism Inhibiting Development of Diabetes in the db Gene Heterozygote

The db gene homozygous, but not heterozygous, mice develop diabetes with severe beta-cell damage. We investigated the molecular mechanism underlying db gene-associated pancreatic beta-cell dysfunction. Islet morphology, beta-cell function, and gene expression profiles specific for pancreatic islet cells were compared among db gene homozygous(db/db), heterozygous (db/m) and unrelated m/m mice. The beta-cell ratio decreased in db/db mice with age, but not in non-diabetic db/m and m/m mice. The islet insulin content was lower, but the triglyceride content was higher in db/db than other mice. The islet cell specific gene expression profiles analyzed by laser capture microdissection method and morphological findings suggested an augmentation of beta-cell apoptosis, oxidative stress and ER stress in db/db mice. Interestingly, insulin I and II, anti-apoptotic bcl-2, and proliferation promoting ERK-1 gene expressions were significantly upregulated in db/m mice. An impaired glucose tolerance was shown in m/m mice fed a high fat diet, but not in db/m mice, in which a higher insulin response and increased beta-cell mass were observed. Expressions of insulin I and II, bcl-2, and ERK-1 gene were increased in db/m mice, but not in m/m fed a high fat diet. The present results strongly suggest that the db gene heterozygote, but not homozygote, acquires a compensatory mechanism suppressing beta-cell apoptosis and augmenting the capacity of beta-cell function.

Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome

BackgroundInflammation may be a mechanism by which high postprandial insulin and glucose responses increase the risk of type 2 diabetes mellitus. ObjectiveWe hypothesized that dietary carbohydrates characterized by different postprandial insulin responses may differentially modify cytokine concentrations in plasma and gene expression in subcutaneous adipose tissue. DesignIndividuals (n = 47) with the metabolic syndrome were randomly assigned to a 12-wk diet with oat and wheat bread and potato (high postprandial insulin response) or rye bread and pasta (low postprandial insulin response). Postprandial glucose and insulin responses to the oat and wheat bread meal and to the rye bread meal were determined in 19 individuals before intervention. ResultsDuring the 12-wk diet, the change in the gene expression of interleukin (IL)-10 receptor α and tumor necrosis factor-α in subcutaneous adipose tissue differed between the groups (P = 0.002 and P = 0.083, respectively). Moreover, the change in fasting plasma concentrations of IL-1β and IL-6 differed between the groups (P = 0.020 and P = 0.055, respectively). In the postprandial challenge, the insulin response to the rye bread meal was lower than that to the oat and wheat bread meal (P < 0.001), whereas there were no differences in the mean blood glucose response. In contrast, plasma glucose concentrations decreased more below fasting concentrations 2.5–3 h after the oat and wheat bread meal than after the rye bread meal. A late postprandial rebound of free fatty acids was detected after the oat and wheat bread meal (P = 0.048). ConclusionsLong-term intake of cereal foods with differing postprandial insulin responses may be a factor that modulates the inflammatory status in individuals with the metabolic syndrome.

Plasma proteome changes in subjects with Type 2 diabetes mellitus with a low or high early insulin response

Circulating proteins contribute to the pathogenesis of T2DM (Type 2 diabetes mellitus) in various ways. The aim of the present study was to investigate variations in plasma protein levels in subjects with T2DM and differences in beta-cell function, characterized by the EIR (early insulin response), and to compare these protein levels with those observed in individuals with NGT (normal glucose tolerance). Ten subjects with NGT+high EIR, ten with T2DM+high EIR, and ten with T2DM+low EIR were selected from the community-based ULSAM (Uppsala Longitudinal Study of Adult Men) cohort. Plasma protein profiling was performed using SELDI-TOF (surface-enhanced laser-desorption ionization-time-of-flight) MS. In total, nine plasma proteins differed between the three study groups (P<0.05, as determined by ANOVA). The levels of two forms of transthyretin, haemoglobin alpha-chain and haemoglobin beta-chain were decreased in plasma from subjects with T2DM compared with subjects with NGT, irrespective of the EIR of the subjects. Apolipoprotein H was decreased in plasma from individuals with T2DM+high EIR compared with subjects with NGT. Four additional unidentified plasma proteins also varied in different ways between the experimental groups. In conclusion, the proteins detected in the present study may be related to the development of beta-cell dysfunction.

Association of n‐6 long‐chain polyunsaturated fatty acids to −866 G/A genotypes of the human uncoupling protein 2 gene in obese children

To investigate the association of plasma fatty acids with the -866 G/A polymorphism of uncoupling protein 2 (UCP2) in obese children. Fatty acid composition of plasma phospholipids and sterol esters were investigated in 80 obese children. Values of dihomo-gamma-linolenic acid (C20:3n-6) were significantly lower in children with the -866 A/A (n = 12) than in those with the -866 G/A (n = 34) or -866 G/G (n = 34) genotype in plasma phospholipids (3.01 [0.42] vs. 3.56 [1.02] vs. 3.53 [0.84], % weight/weight, median [interquartile range], p < 0.05), and were significantly lower in children with the -866 A/A genotype than in the other two groups in plasma sterol esters (0.73 [0.22] vs. 0.92 [0.23] vs. 0.94 [0.25], p < 0.05). Phospholipid C20:3n-6 and arachidonic acid (C20:4n-6) values showed only in children with the -866 G/G and -866 G/A genotypes significant positive correlations with plasma insulin concentrations. Significantly lower values of C20:3n-6 can be detected in obese children with the homozygous (-866 A/A) mutation of UCP2 than in equally obese children with heterozygous mutation or the normal genotype. High glucose-stimulated insulin response is associated with high plasma C20:3n-6 and C20:4n-6 values only in obese children with the G allele of the -866 G/A polymorphism.

Putting your genes on a diet: the molecular effects of carbohydrate

Traditionally, food is thought to influence human health through its nutrient content, whereas drugs are recognized to act through molecular pathways. However, consumption of a meal stimulates the release of numerous hormones that can powerfully affect signal transduction and gene function. The article by Kallio et al (1) in this issue of the Journal highlights this possibility by demonstrating changes in gene expression in individuals consuming diets with different effects on postprandial insulin concentrations. The authors randomly assigned adults with features of the metabolic syndrome to a rye-pasta (low insulin response) or an oat-wheat-potato (high insulin response) diet for 12 wk. The diets were designed to be similar in energy, fiber, and macronutrient contents, although modest differences in fiber, carbohydrate, and protein contents were documented by food records. Gene expression in subcutaneous fat was evaluated at baseline and at 12 wk with microarrays and quantitative polymerase chain reaction. In individuals in the low-insulin-response group, 71 genes showed decreased expression and none showed increased expression. Of particular interest, several down-regulated genes have links to insulin-signaling pathways and apoptosis. In contrast, in individuals in the high-insulin-response group, 62 genes showed increased expression and none showed decreased expression. Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormonesensitive lipase (HSL) and TCF7L2. HSL, a key enzyme in the release of fatty acids from adipose tissue, has been proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to geneticor diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6). In light of these data, proteins involved in lipolysis have become targets of drug development for the treatment of obesity and the metabolic syndrome. Thus, decreased HSL activity might mediate some of the purported benefits of diets designed to lower insulin secretion. The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7). Although the mechanisms involved in disease risk have not been fully elucidated, TCF7L2 affects the Wnt signaling pathway and may be critical for glucagon-like peptide 1 (GLP-1) secretion by intestinal endocrine L cells. Decreased secretion of GLP-1 appears to play a role in the development of type 2 diabetes, and GLP-1 agonists have recently been developed for the treatment of diabetes. The present study has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydrate-containing foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrient-controlled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9). Several methodologic issues should be considered in the interpretation of this study. Microarray analyses have well-known technical limitations and statistical problems, especially when involving small sample sizes (10). The unidirectional change in gene expression within each diet group provides some grounds