Low Insulin Group Research Articles

Effects of Sargassum Glaucescens Algae on Blood Glucose Level in Diabetic Rats With a High-Fat Diet and Streptozotocin

Background: Diabetes medications can have dramatic effects on controlling the disease and achieving the therapeutic goals of people with diabetes, but most of them have side effects. Given the role of brown algae in maintaining blood glucose levels, their investigation can provide valuable information for the control and treatment of type 2 diabetes (T2D). Accordingly, this study investigated the effect of Sargassum glaucescens on blood glucose levels in diabetic rats. Materials and Methods: Forty-six randomly selected rats were assigned to five groups. The control group was fed the normal diet, and diabetic rats were induced by streptozotocin (STZ) and a high-fat diet (HFD). The other groups included the diabetes+low dose insulin group, diabetes+high dose insulin, and diabetic rats that received Sargassum Glaucescens 20% alga powder added to fatty food. Weekly blood glucose, hemoglobin A1c (HbA1c), the amount of drinking water, food consumed, urine volume, glucose tolerance test (GTT), and insulin tolerance test (ITT) underwent measurement. Results: The mean of ITT in the diabetic group was significantly higher than in the control group (P=0.001), which indicates insulin resistance in these groups. The lowest blood glucose concentration was in the high-dose insulin group; weekly blood glucose, GTT, ITT, and HbA1c in the alga group did not change compared to diabetes. However, some indicators, such as HbA1c, were better in the group receiving algae than in the low-dose insulin group. The weight of the group receiving algae increased until the third week, but it decreased after that, and at the end of the study, it was lower in this group than in the control group (P<0.001). Conclusion: The study findings revealed that Sargassum Glaucescens algae had no significant effect on serum glucose, GTT, ITT, or HbA1c in the studied rats.

Impact of Hyperinsulinemia on Long-Term Clinical Outcomes of Percutaneous Coronary Intervention in Patients without Diabetes Who Have Acute Myocardial Syndrome.

Background and ObjectivesHyperinsulinemia plays a key role in the development of cardiovascular impairment in patients with metabolic syndrome. The aim of this study was to evaluate the influence of hyperinsulinemia on long-term clinical outcomes of percutaneous coronary intervention (PCI) in patients without diabetes mellitus who have acute myocardial syndrome (ACS).MethodsBetween March 2016 and January 2019, we enrolled 468 patients with ACS and without diabetes mellitus who received primary PCI. Patients were divided into a low-insulin group (n = 157), medium-insulin group (n = 154), and high-insulin group (n = 157) according to tertiles of fasting insulin level. The primary endpoint was major adverse cardiac events (MACE; all-cause death, non-fatal myocardial infarction, target vessel revascularization [TVR]) at 24 months. The secondary endpoint was angina hospitalization.ResultsPatients in the high-insulin group had an unfavorable prognosis, with a higher rate of MACE (34.39%) than the low-insulin group (22.29%) and medium-insulin group (23.37%) at 24 months (P < 0.05). This difference was mainly driven by the increase in TVR. The high-insulin group also had a higher rate of angina hospitalization than the low-insulin group. Cox proportional hazards regression showed that high-insulin level (hazard ratio [HR] 1.870, 95% confidence interval [CI] 1.202–2.909), small-vessel lesion (HR 1.713, 95% CI 1.111–2.642), bifurcation lesion (HR 3.394, 95% CI 2.033–5.067), SYNTAX score (HR 1.084, 95% CI 1.039–1.130), and stent length (HR 1.017, 95% CI 1.002–1.032) increased the incidence of MACE in patients with ACS and without diabetes who underwent PCI.ConclusionHyperinsulinemia might be a valid predictor of clinical outcomes in patients with ACS undergoing PCI.

Association of peripartum plasma insulin concentration with milk production, colostrum insulin levels, and plasma metabolites of Holstein cows

The main objective of this study was to assess associations between plasma insulin concentration around parturition and production in Holstein cows. Primiparous and multiparous cows (n = 267) were enrolled. Blood samples were collected within 12 h after parturition (d 0), and on d 3 and 10 after calving. In addition, blood samples were collected 7 d before (-7 d) the expected date of parturition and colostrum samples were collected within 8 h after parturition from a subset of cows to measure insulin concentration (n = 47). All samples were harvested from 0630 to 1100 h and were used to quantify insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate. The plasma concentrations of insulin on d -7 and 0 were not correlated with insulin levels in colostrum. Cows were grouped according to plasma insulin concentration based on the median as low insulin (L-INS) or high insulin (H-INS) on d 0 (median = 0.35 ng/mL; range 0.2 to 1.2), 3 (median = 0.32 ng/mL; range 0.2 to 1.6), and 10 (median = 0.30 ng/mL; range 0.2 to 0.8). We detected that cows in the L-INS group on d 0 (L-INS = 0.57 ± 0.02; H-INS = 0.49 ± 0.02 mmol/L), d 3 (L-INS = 0.56 ± 0.02; H-INS = 0.49 ± 0.02 mmol/L), and d 10 (L-INS = 0.61 ± 0.03; H-INS = 0.55 ± 0.03 mmol/L) had higher NEFA concentrations compared with cows in the H-INS group. Compared with H-INS cows, milk yield was higher for cows classified as L-INS on d 0 (L-INS = 40.75 ± 0.69; H-INS = 38.41 ± 0.64 kg) and d 10 (L-INS = 40.95 ± 0.74; H-INS = 38.66 ± 0.64 kg). Moreover, fat-corrected milk was higher for cows classified as L-INS on d 0 (L-INS = 40.59 ± 2.36; H-INS = 37.73 ± 2.31 kg) and d 10 (L-INS = 41.00 ± 2.42; H-INS = 38.65 ± 2.28 kg) compared with H-INS cows, and energy-corrected milk was higher for L-INS cows compared with H-INS cows regardless of the day (d 0, L-INS = 44.50 ± 0.70 vs. H-INS = 41.67 ± 0.64 kg; d 3, L-INS = 43.65 ± 0.74 vs. H-INS = 40.88 ± 0.72 kg; d 10, L-INS = 44.09 ± 0.73 vs. H-INS = 40.55 ± 0.68 kg). We conclude that low plasma insulin concentration during early lactation is associated with higher milk yield in the long term.

Association between high-fasting insulin levels and metabolic syndrome in non-diabetic middle-aged and elderly populations: a community-based study in Taiwan

ObjectivesWe aimed to determine the association between fasting insulin (FI) levels and metabolic syndrome (MetS) in non-diabetic middle-aged and elderly adults in a community in Taiwan.DesignCross-sectional observational study.SettingCommunity-based investigation in...

Insulin promotes preantral follicle growth and antrum formation through temporal expression of genes regulating steroidogenesis and water transport in the cat.

The aims of the present study were to determine the effects of insulin, invitro, on: (1) the viability and growth of domestic cat ovarian follicles; (2) mRNA expression of genes regulating steroidogenesis (cytochrome P450 family 17 subfamily, A polypeptide 1 (Cyp17a1), cytochrome P450 family 19 subfamily, A polypeptide 1 (Cyp19a1) and steroidogenic acute regulatory protein (Star)) and water transport (aquaporins (AQPs) Aqp1, Aqp3, Aqp7, Aqp9); and (3) steroid production (17β-oestradiol (E2), progesterone (P4), androstenedione (A4)). Cat secondary follicles were isolated from ovarian cortices and cultured in 0 (Control), 1 or 10µgmL-1 insulin for 14 days (Day 0=culture onset). Follicle and oocyte viability (based on neutral red staining), diameter and antrum formation were assessed every 72h and at the end of incubation (Day 14). Expression of steroidogenic and water transport genes was evaluated on Days 0, 6 and 12, and E2, P4 and A4 concentrations in the culture medium were determined on Day 12. By Day 14, 1 and 10µgmL-1 insulin had significantly promoted (P<0.05) both antrum formation in a mean (±s.e.m.) 26.9±9.0% and 78.0±10.0% of follicles respectively, and follicle growth (diameter 151.4±4.5 and 169.9±10.5µm respectively) compared with Control (antrum formation in 3.3±3.3% of follicles and follicle diameter 129.1±6.6µm). High insulin (10µgmL-1) treatment increased follicle viability compared with Control (86.0±9.8% vs 38.1±10.9% respectively; P<0.05). However, insulin had no beneficial effect (P>0.05) on oocyte diameter. Cyp17a1 expression on Days 6 and 12 was higher (P<0.05) in follicles cultured in the low (1µgmL-1) compared with high (10µgmL-1) insulin treatment, with no significant difference between low or high insulin vs Control groups. Star expression was higher (P<0.01) in the low insulin compared with Control group on Day 6, but Star was undetectable in the high insulin group by Day 12. Compared with high insulin, low insulin increased (P<0.05) Aqp1 expression on Day 6, but there were no significant differences between these two groups on Day 12. In contrast, high insulin decreased (P<0.05) Aqp9 transcript levels compared with Control. Only P4 production was affected by insulin, with P4 concentrations in the medium being higher (P<0.05) in the low compared with high insulin and Control groups. In summary, the findings indicate that insulin promotes cat ovarian follicle growth and survival invitro, including enhanced antrum formation, with the likely mechanism involving temporal expression of Cyp17a1, Star and Aqp9 genes.

The effect of AdipoRon on insulin sensitivity of mouse skeletal muscle cells and its mechanism

To observe the effect of AdipoRon, an adiponin receptor agonist, on insulin sensitivity in mouse myoblast cell line (C2C12) and to explore its mechanism. C2C12 was induced to differentiate into myoblasts by using horse serum. Then the cells were divided into 6 groups (9 double wells):blank control group, high dose AdipoRon group, low dose AdipoRon group, insulin group and the low dose AdipoRon with PI3K inhibitor (phosphatidylinositol 3 kinase) group and the insulin with PI3K inhibitor group. After cultured for 12 h, the supernatant was collected and glucose consumption was measured. Cell proliferation was tested by using CCK8. In the 6-well plate, C2C12 was induced to differentiate into myoblasts. The drug was incubated for 12 h and the mRNA level of GLUT4 was detected by RT-PCR. Compared with the blank control group, the levels of glucose consumption in high dose AdipoRon group, low dose AdipoRon group and insulin group was increased significantly (P<0.05). After adding PI3K inhibitor, the levels of glucose consumption in the above mentioned three groups were not different from that in blank control group. high dose AdipoRon group, low dose AdipoRon group and insulin group had proliferation, but only the insulin group was statistically significant (P<0.05). Compared with the control group, the levels of GLUT4 mRNA in AdipoRon high dose group, low dose AdipoRon group and insulin group were all higher than those in control group (P<0.05). After adding PI3K inhibitor, GLUT4 mRNA level was not statistically significant compared with blank control group. AdipoRon can increase the consumption of glucose without affecting cell proliferation, which may play a role in improving insulin sensitivity, but the specific mechanism remains to be further studied.

Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct

Background and aimsThe effects of glucocorticoids on fuel metabolism are complex. Acute glucocorticoid excess promotes lipolysis but chronic glucocorticoid excess causes visceral fat accumulation. We hypothesized that interactions between cortisol and insulin and adrenaline account for these conflicting results. We tested the effect of cortisol on lipolysis and glucose production with and without insulin and adrenaline in humans both in vivo and in vitro.Materials and methodsA total of 20 healthy men were randomized to low and high insulin groups (both n = 10). Subjects attended on 3 occasions and received low (c. 150 nM), medium (c. 400 nM) or high (c. 1400 nM) cortisol infusion in a randomized crossover design. Deuterated glucose and glycerol were infused intravenously along with a pancreatic clamp (somatostatin with replacement of glucagon, insulin and growth hormone) and adrenaline. Subcutaneous adipose tissue was obtained for analysis. In parallel, the effect of cortisol on lipolysis was tested in paired primary cultures of human subcutaneous and visceral adipocytes.Results In vivo, high cortisol increased lipolysis only in the presence of high insulin and/or adrenaline but did not alter glucose kinetics. High cortisol increased adipose mRNA levels of ATGL, HSL and CGI‐58 and suppressed G0S2. In vitro, high cortisol increased lipolysis in the presence of insulin in subcutaneous, but not visceral, adipocytes.ConclusionsThe acute lipolytic effects of cortisol require supraphysiological concentrations, are dependent on insulin and adrenaline and are observed only in subcutaneous adipose tissue. The resistance of visceral adipose tissue to cortisol's lipolytic effects may contribute to the central fat accumulation observed with chronic glucocorticoid excess.

The Relation between Serum Uric Acid and HbA1c Is Dependent upon Hyperinsulinemia in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

Objective. The aim of our study was to explore the dependent condition of the relationship between uric acid and blood glucose in type 2 diabetes. Research Design and Methods. We measured the HbA1c, serum uric acid, creatinine, lipids profiles, and so forth of 605 newly diagnosed type 2 diabetes patients, and oral glucose tolerance tests (OGTTs) were performed on each patient. The population was divided into high and low insulin groups. Multiple linear regression analyses were conducted to assess the relationship between uric acid and HbA1c. Results. Serum uric acid and HbA1c levels were low in newly diagnosed type 2 diabetes patients. However, we found no significant relationship between uric acid and HbA1c by regression analysis after adjusting total insulin. The concentration of uric acid was inversely correlated with HbA1c in the high insulin group, regardless of patient sex. However, no associations were found in low insulin group. Conclusions. The negative correlation between uric acid and HbA1c is conditional in newly diagnosed type 2 diabetes patients and is related to hyperinsulinemia. Therefore, uric acid is likely only useful as a biomarker of blood glucose in patients exhibiting hyperinsulinemia.

Body Composition and Metabolic Risk Variables for Obesity in Korean Healthy Women

Objective: To investigate which indices to relate with metabolic risk among body composition. Design and methods: As a cross sectional study, a total of 47 healthy Korean women aged 40.36 years, BMI 25.59 kg/m2, were assessed their BMI, percent of body fat (BIA), fat mass by DXA, adipose tissue (CT), fasting insulin, free fatty acid, cholesterol, triglyceride, HDL cholesterol, fasting plasma glucose, and HOMA IR index. Results: Neither dyslipidemia nor hyperglycaemia has any relation with central fatness indicators & BMI. Fasting insulin is related with %BF* after correction for age. Dyslipidemia and hyperglycaemia tend to be greater in low insulin group. Among body composition, BMI, ** fat mass (DXA) **, %BF** except VAT, SAT, and V/S ratio of high insulin group are significantly higher than those of low insulin group. Although not significant, V/S ratio is likely to be higher in low insulin group. (*: p<0.05, **:p<0.01) Conclusions: V/S ratio maybe a determinant to metabolic risks variables in healthy Korean women. Controlled lager cohort study would be considered in the future, to prove the association between SAT and metabolic derangement. In conclusion, %BF through BIA is considered as the major determinant to fasting insulin in Korean women.

Assessment of metabolic status in young Japanese females using postprandial glucose and insulin levels.

Lifestyle-related diseases develop through the accumulation of undesirable lifestyle habits both prior to the onset of disease as well as during normal healthy life. Accordingly, early detection of, and intervention in, metabolic disorders is desirable, but is hampered by the lack of an established evaluation index for young individuals. The purpose of this study was to investigate the utility of a biomarker of health in young female subjects. The subjects were young healthy Japanese females in whom energy expenditure was measured for a period of 210 min after a test meal. In addition, Δplasma glucose and Δserum insulin were calculated from the fasting and 30 min values. ΔPlasma glucose and Δserum insulin levels varied widely compared to fasting levels. Both the area under the curve of carbohydrate oxidation rate and serum free fatty acid levels were higher in individuals in the high Δplasma glucose group. Moreover, Δplasma glucose was higher in individuals in the high Δserum insulin group than in the low Δserum insulin group. We conclude that nutritional balanced liquid loading test using Δplasma glucose and Δserum insulin as the evaluation index is useful for the detection of primary metabolic disorders in young females.

Association of plasma insulin concentration to fatty acid distribution between milk fat and membrane synthesis

We examined the association between plasma insulin concentration and fatty acid distribution to milk fat and membrane fractions (triglyceride and phospholipid, respectively) in dairy cows. Thirty-seven Holstein cows at 60 to 70 d postpartum were synchronized by 2 PGF2α injections 14 d apart. Plasma samples were taken before morning and evening milkings and milk samples were obtained at morning milking. Plasma insulin concentrations were determined and cows were retrospectively assigned to low insulin (LI; 2.8±0.2ng/mL, n=6) or high insulin (HI; 5.9±0.6ng/mL, n=7) experimental groups. Fatty acid analysis of milk samples demonstrated a possible association between plasma insulin concentration and the fatty acid composition in phospholipid and triglyceride fractions. In the HI group, monounsaturated fatty acid concentration tended to be higher in the triglyceride (Tg) fraction than the phospholipids (Pl) fraction. In the LI group, the concentrations of short- and medium-chain saturated fatty acids (<16 carbon chain length), considered de novo-synthesized fatty acids, were higher in the triglyceride fraction than the phospholipid fraction. These results imply that the primary source of saturated fatty acids for phospholipid synthesis, in both HI and LI groups, is the circulation, as reflected by a higher concentration of longer saturated fatty acids (>16 carbon chain length) in the phospholipid fraction. Finally, the phospholipid-to-triglyceride ratio was higher in the HI group than in the LI group. Together, the results indicate that fatty acid distribution between phospholipid (membrane) and triglyceride (fat) synthesis by the mammary gland is associated with fatty acid length, degree of unsaturation, and origin, and might be subject to metabolic hormone regulation. Furthermore, a lower triglyceride-to-phospholipid ratio in the HI group implies that high plasma insulin and low milk fat concentrations are associated with a shift in the size distribution of milk fat globules.

The level of fasting serum insulin, but not adiponectin, is associated with the prognosis of early stage hepatocellular carcinoma

Impaired glucose tolerance influences the prognosis of hepatocellular carcinoma (HCC), but this mechanism is still not fully understood. We investigated the impact of the fasting serum levels of insulin and adiponectin on the prognosis of HCC and its recurrence. One hundred and forty patients with newly diagnosed HCC were enrolled in the prognosis study. Their fasting serum levels of insulin and adiponectin were determined. Of 140 patients, 59 patients who underwent curative treatment were subjected to analysis of the recurrence-free survival. The 140 patients were divided into two groups by the 50th percentile value of insulin (7.73 microIU/ ml) or total adiponectin (6.95 microg/ml). Kaplan-Meier analysis indicated that high insulin group (>7.73 microIU/ml) exhibited a significantly poorer prognosis than low insulin group (<7.73 microIU/ml) in early stage HCC (P=0.018). In contrast, the level of total adiponectin had no impact on the prognosis of HCC. Multivariate analysis indicated that fasting hyper-insulinemia was an independent risk factor for a poorer prognosis in early stage HCC (P=0.044). Likewise, Kaplan-Meier analysis indicated that the recurrence-free survival of high insulin group was significantly lower than that of low insulin group (P=0.017). The level of total adiponectin had no impact on the recurrence-free survival of HCC. Multivariate analysis indicated that fasting hyperinsulinemia was an independent risk factor for the lower recurrence-free survival of HCC (P=0.049). In conclusion, our study suggests that the fasting insulin level affects the clinical course of early stage HCC.

Insulin-dependent actions of pioglitazone in newly diagnosed, drug naïve patients with type 2 diabetes

The aim of this study was to study the effects of pioglitazone on several diabetic parameters with subjects possessing distinct levels of insulin. Treatment naive patients with type 2 diabetes received 15-30 mg/day pioglitazone monotherapy. At 3 months, levels of insulin, C-peptide, HbA1c, HOMA-R, HOMA-B and BMI were compared with those at baseline between the low (below 5.9 microU/ml, n = 48), medium (11.9-6 microU/ml n = 39) and high (above 12 microU/ml, n = 33) insulin groups. At baseline, differences existed in the levels of HbA1c, insulin, C-peptide, HOMA-R, HOMA-B, and BMI between these groups. In the high-insulin group significant reductions of insulin/C-peptide levels were observed, while in the low-insulin group significant increases of insulin/C-peptide were observed. In the medium-insulin group, no significant changes were observed. In contrast, the HbA1c levels significantly and similarly decreased in all the groups. Significant correlations between the changes of insulin/C-peptide levels with pioglitazone and the baseline insulin/C-peptide levels were observed. HOMA-R showed greater reductions in the high-insulin group, while HOMA-B showed greater increases in the low-insulin group in comparison to other groups. Multiple regression analysis revealed that the baseline insulin level is the predominant determinant of the changes of insulin levels with pioglitazone. These results suggest that pioglitazone appears to have two effects: to reduce insulin resistance (and lower insulin) and to improve beta-cell function (and increase insulin). The predominance of these effects appears to be determined by the insulin levels. Based on these data, a novel physiological model showing that pioglitazone may shift the natural history of diabetes toward an earlier stage (rejuvenation of beta-cell function) will be presented.

Relation of Plasma Obestatin Levels to BMI, Gender, Age and Insulin

Obestatin is supposed to be involved in nutrient homeostasis. Therefore, basal plasma obestatin levels were investigated in 321 normal weight and obese subjects in relation to body mass index, gender, age, insulin concentrations, and type 2 diabetes mellitus. Additionally, postprandial obestatin levels were determined in 20 normal weight subjects. Basal obestatin levels in females were higher compared to males (193.6+/-5.8 vs. 140.6+/-5.1 pg/ml). Obestatin levels correlated inversely and significantly with body mass index (f: r=-0.632, p<0.001; m: r=-0.487, p<0.001) and basal insulin levels (f: r=-0.536, p<0.001; m: r=-0.320, p=0.008) in females and males. However, in a multiple regression analysis as well as in a matched comparison of a low and high insulin group no significant relationship between insulin and obestatin levels was observed in nondiabetics. On the other hand, inclusion of type 2 diabetics with higher insulin levels resulted in a significant inverse correlation. Obestatin levels were independent of age in both sexes. In patients with type 2 diabetes mellitus basal obestatin levels were not different compared to nondiabetic subjects when matched for gender, body mass index, and insulin. In normal weight subjects, postprandial obestatin levels showed a significant decrease between 60 and 90 minutes rising to basal levels thereafter. The present data demonstrate a relation of plasma obestatin levels to body weight, gender and food intake, but not to age. The inverse relationship with insulin might depend on the level of hyperinsulinemia. The present data are compatible with a potential role of obestatin in nutrient regulation.

Supraphysiological hyperinsulinemia acutely increases hypothalamic-pituitary-adrenal secretory activity in humans.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in association with hyperinsulinemia is frequently found in patients with type 1 and type 2 diabetes mellitus and in subjects with abdominal adiposity. We questioned whether insulin could cause HPA axis activation and, if so, whether this insulin action may arise at the adrenal level or at a central (i.e. hypothalamic-pituitary) level. Experiments lasting for 6 h each were done in 30 lean healthy men. In 15 men, insulin was infused at a rate of 1.5 mU min(-1) kg(-1). Plasma glucose concentration was held constant during an euglycemic clamp session and was decreased stepwise in a hypoglycemic clamp session. The sequence of the 2 clamp sessions was random, and a 4-weeks recovery period was allowed between the two sessions. The protocol was essentially the same in another 15 men, with the exception that insulin was infused at a rate of 15.0 mU min(-1) kg(-1). During the euglycemic clamp sessions, we found plasma ACTH levels to increase only in the high-, but not in the low-insulin group (group by time interaction, P < 0.01); serum cortisol levels were greater in the high than in the low-insulin group (P < 0.02). In the hypoglycemic clamp sessions, plasma ACTH levels increased in the same pattern in the 2 groups; serum cortisol was greater in the high than in the low-insulin group at the beginning of the clamp (plasma glucose approximately 4.1 mmol/L; P < 0.05). Our results demonstrate that insulin acutely stimulates the HPA secretory activity in humans. The pattern suggests an effect of insulin at both peripheral and central levels of the HPA axis.

Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: The Bogalusa Heart Study

Background Insulin resistance, often associated with obesity, is hypothesized to be involved in the pathogenesis of essential hypertension and may relate to increased left ventricular mass (LVM). Methods We examined correlations between echocardiographic LVM and fasting blood glucose and insulin levels in a cross-section of 216 black and white healthy children and young adults aged 13 to 27 years in Bogalusa, Louisiana. Anthropometric measurements and blood pressure readings were also obtained. Results Positive bivariate correlation was found between fasting blood glucose level and LVM corrected for growth (LVMC) (LVMC = LVM/Height 2.7) with all race/sex groups combined ( r = 0.17, P ≤ .03). Multivariate analyses in a model including race, sex, age, and measures of body size showed no significant correlations between fasting blood glucose level, insulin level, and LVMC. However, when patients were ranked in terciles by fasting insulin level and within each tercile by subscapular skinfold thickness or weight tercile, increasing LVMC with increasing insulin level was found in the highest subscapular skinfold thickness and weight terciles. The largest difference was between high and low insulin groups ( P ≤ .03). When grouped by systolic blood pressure tercile, there was no difference in LVMC with increasing fasting insulin tercile. We concluded that in heavier individuals, increased insulin levels may be a risk factor for the accumulation of increased LVMC independent of any relation among insulin, obesity, and blood pressure. (Am Heart J 1999;138:122-7.)

Insulin inhibition of 5′ adenosine monophosphate—activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation

Acetyl coenzyme A (CoA) carboxylase (ACC) is an important regulator of fatty acid oxidation in the heart, since it produces malonyl CoA, a potent inhibitor of mitochondrial fatty acid uptake. Under conditions of metabolic stress, 5′adenosine monophosphate—activated protein kinase (AMPK), which is highly expressed in cardiac muscle, can phosphorylate and decrease ACC activity. In this study, we determined if fatty acid oxidation in the heart could be regulated by insulin, due to alterations in AMPK regulation of ACC activity. Isolated working rat hearts were perfused with Krebs-Henseleit solution containing 11 mmol/L glucose, 0.4 mmol/L [9,10- 3H]palmitate, and either 100 μU/mL insulin or 1,000 μU/mL insulin. Increasing insulin concentration resulted in a decrease in fatty acid oxidation rates ( P < .05), a decrease in AMPK activity ( P < .05), and an increase in ACC activity ( P < .05) compared with the low-insulin group. A negative correlation was observed between AMPK and ACC activity ( r = −.76). We conclude that insulin, acting through inhibition of AMPK and stimulation of ACC, is capable of inhibiting myocardial fatty acid oxidation.

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group.

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance.

Changes of lipolytic enzymes cluster with insulin resistance syndrome

The activities of hepatic and lipoprotein lipase and the levels of lipo- and apoproteins were compared in two groups of normoglycaemic men representing the highest (n = 18) and lowest (n = 15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2 +/- 4.0 vs 20 +/- 5.8 mumol NEFA.ml-1.h-1, p < 0.001); hepatic lipase activity did not differ between the two groups (24.2 +/- 11 vs 18.0 +/- 5.3 mumol NEFA.ml-1.h-1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66% as compared to the low insulin group (0.75 +/- 0.57 vs 1.25 +/- 0.65, p < 0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61 +/- 0.57 vs 0.86 +/- 0.26 mmol/l, p < 0.001 and 1.00 +/- 0.47 vs 0.36 +/- 0.16 mmol/l, p < 0.001, respectively) whereas HDL cholesterol and HDL2 cholesterol were lower (1.20 +/- 0.30 vs 1.43 +/- 0.22 mmol/l, p < 0.05 and 0.49 +/- 0.21 vs 0.71 +/- 0.17 mmol/l, p < 0.05, respectively). Total cholesterol, LDL cholesterol or HDL3 cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258 +/- 7 vs 265 +/- 6 A, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of insulin, race, and hypertension with hemodynamic reactivity to a behavioral challenge

Insulin is a modulator of blood pressure and may play a role in the pathogenesis of hypertension. This study examined the relationship between fasting insulin level and cardiovascular reactivity in hypertensive and normotensive black and white patients. Eighty-one patients were studied after 3 days of hospitalization on an isocaloric diet providing 200 mmol Na+ and 100 mmol K+ per day. Fasting insulin levels were determined on the morning of the second hospital day; a median split was used to determine high- and low-insulin groups. On the next day of hospitalization we examined blood pressure and hemodynamic responses to a speaking challenge. Hemodynamic responses were determined with impedance cardiography. Reactivity was studied as the percentage change from resting baseline. There were significant race by blood pressure level interactions for systolic and diastolic blood pressure reactivity (P < or = .01). Black hypertensives showed more blood pressure reactivity than either the white hypertensives or the white normotensives; black normotensives had less blood pressure reactivity than the other groups. Insulin grouping interacted with blood pressure level and race on the reactivity of the underlying hemodynamic measures (total peripheral resistance, stroke volume, and heart rate; P < or = .02). Fasting insulin level had no relationship to blood pressure reactivity. On the other hand, insulin level interacted with blood pressure level and race on the underlying hemodynamics controlling blood pressure, namely total peripheral resistance and stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)