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PubMed1978

Change of insulin dosage, circulating free and bound insulin and insulin antibodies on transferring diabetics from conventional to highly purified porcine insulin.

Fifty-eight patients on long term conventional mainly bovine insulins have been transferred to highly purified porcine insulin preparations. There was an overall reduction of 22% in daily insulin dosage and improved diabetic control as shown by decreased blood glucose concentration. Increased concentrations of serum free insulin and falls in serum bound insulin levels were also found. There were reductions in the serum binding capacities and affinity constants on changeover from conventional to highly purified insulin due to a combination of the effects of differential conventional/purified porcine binding and the substitution of a low antigenicity insulin. However, 12 of the patients receiving higher doses of insulin experienced marked hypoglycaemic reactions immediately on insulin changeover despite initial dosage reductions of 30% and prior to any changes in antibody characteristics.

Adolescent↗
PubMed2002

Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes.

OBJECTIVE: To compare the safety and efficacy of insulin aspart (IAsp), buffered regular insulin (BR), and insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: After completing a 4-week run-in period with BR, 146 adult patients with type 1 diabetes (with pretrial CSII experience) were randomly assigned (2:2:1) to CSII treatment with IAsp, BR, or lispro for 16 weeks in a multicenter, open-label, randomized, parallel-group study. Bolus insulin doses were administered 30 min before meals (BR) or immediately before meals (IAsp or lispro). RESULTS: Treatment groups had similar baseline HbA(1c) (7.3% +/- 0.7 for IAsp, 7.5% +/- 0.8 for BR, and 7.3% +/- 0.7 for lispro). After 16 weeks of treatment, HbA1c values were relatively unchanged from baseline, and the mean changes in baseline HbA1c values were not significantly different between the three groups (0.00 +/- 0.51, 0.15 +/- 0.63, and 0.18 +/- 0.84 for the IAsp, BR, and lispro groups, respectively). The rates of hypoglycemic episodes (blood glucose <50 mg/dl) per patient per month were similar (3.7, 4.8, and 4.4 for the IAsp, BR, and lispro groups, respectively). Clogs/blockages in pumps or infusion sets were infrequent; most subjects (76, 83, and 75% in the IAsp, BR, and lispro groups, respectively) had < or = 1 clog or blockage per 4 weeks during the trial. CONCLUSIONS: Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps.

Adult↗
PubMed1979

Insulin action in isolated fat cells. II. Effects of divalent cations on stimulation by insulin of protein synthesis, on inhibition of lipolysis by insulin, and on the binding of 125I-labelled insulin to isolated fat cells.

The effects of ommission of Ca2+ and Mg2+ from the incubation medium on three aspects of insulin action in isolated fat cells have been investigated. In the (Ca2+ + Mg2+)-free incubation medium incorporation of L-[14C]leucine into fat cell protein was reduced in the absence of insulin. Insulin stimulated L-[14C]leucine incorporation only in the presence of added CaCl2 or MgCl2. Incubation of the cells in the (Ca2+ + Mg2+)-free medium reduced but did not abolish the ability of adrenaline to stimulate lipolysis or the ability of insulin to inhibit the adrenaline-stimulated lipolysis. Specific binding of 125I-labelled insulin to the fat cells was reduced in the absence of Ca2+ and Mg2+ but was not abolished, even in the presence of EDTA. Ca2+ was routinely the most effective divalent cation in supporting these aspects of insulin action, but similar responses were obtained with Mg2+, Sr2+ and Ba2+. Since insulin still binds to the cells under conditions in which some of the cellular effects of the hormone are abolished, it is suggested that divalent cations may have a role, either direct or indirect, in the processes linking the insulin-insulin receptor complex to certain effector systems in the cells. It is tentatively suggested that this action occurs at the level of the fat cell plasma membrane.

Adipose Tissue↗
PubMed1995

Tyrosine kinase activity of a chimeric insulin-like-growth-factor-1 receptor containing the insulin receptor C-terminal domain. Comparison with the tyrosine kinase activities of the insulin and insulin-like-growth-factor-1 receptors using a cell-free system.

In a previous study, we showed that a chimeric insulin-like-growth-factor-1 (IGF-1) receptor, with the beta subunit C-terminal part of the insulin receptor was more efficient in stimulating glycogen synthesis and p44mapk activity compared to the wild-type IFG-1 receptor [Tartare, S., Mothe, I., Kowalski-Chauvel, A., Breittmayer, J.-P., Ballotti, R. & Van Obberghen, E. (1994) J. Biol. Chem. 269, 11449-11455]. These data indicate that the receptor C-terminal domain plays an important role in the transmission of biological effects. To understand the molecular basis of the differences in receptor specificity, we studied the characteristics of insulin, IGF-1 and chimeric receptor tyrosine kinase activities in a cell-free system. We found that, compared to wild-type insulin and IGF-1 receptors, the chimeric receptor showed a decrease in (a) autophosphorylation, (b) tyrosine kinase activity towards insulin receptor substrate-1 and the insulin receptor-(1142-1158)-peptide, and (c) the ability to activate phosphatidylinositol 3-kinase. However, for all the effects measured in a cell-free system, the chimeric receptor displayed an increased response to IGF-1 compared to the native IGF-1 receptor. Concerning the cation dependence of the tyrosine kinase activity, we showed that, at 10 mM Mg2+, the ligand-stimulated phosphorylation of poly(Glu80Tyr20) by both insulin receptor and chimeric receptor was increased by Mn2+. Conversely at 50 mM Mg2+, the chimeric receptor behaved like the IGF-1 receptor, since the presence of Mn2+ decreased the stimulatory effect of IGF-1 on their kinase activity. Furthermore, the Km of the chimeric receptor for ATP was increased compared to the wild-type receptors. These data demonstrate that the replacement of the C-terminal tail of the IGF-1 receptor by that of the insulin receptor has changed the receptor characteristics studied in a cell-free system. Our findings indicate that the C-terminal domain of the insulin receptor beta subunit plays a key role in regulation of the tyrosine kinase activity. The fine-tuning of the tyrosine kinase by the C-terminal tail could participate in the receptor specificity.

Adenosine Triphosphate↗
PubMed1992

Insulin receptor gene expression during development: developmental regulation of insulin receptor mRNA abundance in embryonic rat liver and yolk sac, developmental regulation of insulin receptor gene splicing, and comparison to abundance of insulin-like growth factor 1 receptor mRNA.

Insulin gene expression has been demonstrated in nonpancreatic tissues early in development, suggesting that this hormone might have actions significant for the differentiating embryo. Because such actions imply ligand-receptor binding, we quantified mRNAs encoding the two known forms of insulin receptor in rat liver and yolk sac, two endodermally derived tissues shown to express insulin genes, between gestation days (E) 13 and E21 (mid-organogenesis to parturition). Because of its presumed importance for fetal growth, we estimated the abundance of mRNA encoding insulin-like growth factor 1 (IGF 1) receptor in the same samples for comparison. The abundance of insulin receptor mRNA exceeded that for IGF 1 receptor mRNA in liver and yolk sac at all times studied. This difference was greater in liver, where insulin receptor mRNAs were three to more than 50 times more abundant than IGF 1 receptor mRNA on gestation days E13-E16, times which antedate the development of significant hepatic metabolic actions of insulin. The marked abundance of mRNAs encoding insulin receptors is consistent with the hypothesis that insulin has significant actions in specific tissues during the organogenic period.

Animals↗
PubMed1998

Reconstitution of insulin signaling pathways in rat 3Y1 cells lacking insulin receptor and insulin receptor substrate-1. Evidence that activation of Akt is insufficient for insulin-stimulated glycogen synthesis or glucose uptake in rat 3Y1 cells.

Rat 3Y1 cells have endogenous insulin-like growth factor-1 receptors and insulin receptor substrate (IRS)-2, but lack both insulin receptor (IR) and IRS-1. To investigate the role of IR and IRS-1 in effects of insulin, we transfected IR and IRS-1 expression plasmids into cells and reconstituted the insulin signaling pathways. 3Y1 cells stably expressing the c-myc epitope-tagged glucose transporter type 4 (3Y1-GLUT4myc) exhibit no effects of insulin, at physiological concentrations. The 3Y1-GLUT4myc-IR cells expressing GLUT4myc and IR responded to phosphatidylinositol 3,4, 5-trisphosphate (PI-3,4,5-P3) accumulation, Akt activation, the stimulation of DNA synthesis, and membrane ruffling but not to glycogen synthesis, glucose uptake, or GLUT4myc translocation. The further expression of IRS-1 in 3Y1-GLUT4myc-IR cells led to stimulation of glycogen synthesis but not to glucose uptake or GLUT4myc translocation in response to insulin, although NaF or phorbol 12-myristate 13-acetate did trigger GLUT4myc translocation in the cells. These results suggest that, in rat 3Y1 cells, (i) IRS-1 is essential for insulin-stimulated glycogen synthesis but not for DNA synthesis, PI-3,4,5-P3 accumulation, Akt phosphorylation, or membrane ruffling, and (ii) the accumulation of PI-3,4,5-P3 and activation of Akt are insufficient for glycogen synthesis, glucose uptake or for GLUT4 translocation.

Amino Acid Sequence↗
PubMed1986

Transfer from porcine insulin to human insulin in insulin-dependent diabetes mellitus: effects on insulin binding to IgG and glycemic control.

Thirty type I diabetic patients who were treated for at least 2 years with a combination of regular and lente monocomponent porcine insulins were allocated in a double-blind study to either continued porcine insulin treatment or a transfer to the corresponding semi-synthetic human insulins. Insulin binding to IgG measured by an immunoelectrophoretic method, was followed at 3-month intervals for 1 year, and did not change after the transfer. The glycemic control, as assessed by hemoglobin A1 levels, tended to deteriorate in the human insulin group during the first 3 months of the trial and then return to the baseline level. It is concluded that a transfer from highly purified porcine insulin to human insulin apparently does not change the insulin binding to IgG in already sensitized patients.

Adult↗
PubMed1978

The relationship between circulating free and bound insulin, insulin antibodies, insulin dosage and diabetic control in insulin treated diabetics.

Free and bound insulin concentrations, blood glucose and anti-insulin antibody binding characteristics have been determined in 100 insulin treated diabetics; medium serum free insulin was 11 mU/l when fasting and rose to 30 mU/l after the mid-day meal. Significant correlation between blood glucose and serum free (but not bound) insulin was found. No relationship between insulin antibodies and daily insulin dose or diabetic control were found, nor a relationship between free insulin and antibody characteristics.

Adolescent↗
PubMedDate not supplied

Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group.

OBJECTIVE: To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life. DESIGN: Randomized clinical trial. SETTING: Seven Veterans Affairs medical centers. PATIENTS: One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above. INTERVENTION: Intensive therapy (IIP or MDI) for 1 year. MAIN OUTCOME MEASURES: Hemoglobin A1c and blood glucose levels. RESULTS: Blood glucose levels declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump. CONCLUSIONS: Intensive insulin therapy with IIP and MDI is effective in controlling non-insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.

Adult↗
PubMed1999

Antiinsulin receptor autoantibodies induce insulin receptors to constitutively associate with insulin receptor substrate-1 and -2 and cause severe cell resistance to both insulin and insulin-like growth factor I.

We report here that antiinsulin receptor (anti-IR) autoantibodies (AIRs) from a newly diagnosed patient with type B syndrome of insulin resistance induced cellular resistance not only to insulin but also to insulin-like growth factor I (IGF-I) for the stimulation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase activities and of glycogen and DNA syntheses. The molecular mechanisms of this dual resistance were investigated. Patient AIRs bound the IR at the insulin-binding site and caused insulin resistance at the IR level by inducing a 50% decrease in cell surface IRs and a severe defect in the tyrosine kinase activity of the residual IRs, manifested by a loss of insulin-stimulated IR autophosphorylation and IR substrate-1 (IRS-1)/IRS-2 phosphorylation. In contrast, cell resistance to IGF-I occurred at a step distal to IGF-I receptors (IGF-IRs), as AIRs altered neither IGF-I binding nor IGF-I-induced IGF-IR autophosphorylation, but inhibited the ability of IGF-IRs to mediate tyrosine phosphorylation of IRS-1 and IRS-2 in response to IGF-I. Coimmunoprecipitation assays showed that in AIR-treated cells, IRs, but not IGF-IRs, were constitutively associated with IRS-1 and IRS-2, strongly suggesting that AIR-desensitized IRs impeded IGF-I action by sequestering IRS-1 and IRS-2. Accordingly, AIRs had no effect on the stimulation of mitogen-activated protein kinase activity or DNA synthesis by vanadyl sulfate, FCS, epidermal growth factor, or platelet-derived growth factor, all of which activate signaling pathways independent of IRS-1/IRS-2. Thus, AIRs induced cell resistance to both insulin and IGF-I through a novel mechanism involving a constitutive and stable association of IRS-1 and IRS-2 with the IR.

Aged↗
PubMed1981

Mechanism of action of insulin and insulin analogues. A comparison of the hepatic and peripheral effects on glucose turnover of insulin, proinsulin and three insulin analogues modified at positions A1 and B29.

A [14C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A1, B29-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A1-B29 crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.

Animals↗
PubMed1977

Structure and activity of insulin, XV[1-5]. Further evidence for the importance of arginine residue B22 in the activity of insulin. Semisyntheses of despentapeptide-(B23 - 30)-insulins varied in B22 using desnonapeptide-(B22 - 30)-insulin and tetrapeptides.

Insulin hexamethyl ester was digested by trypsin. The resulting desoctapeptide-(B23 - 30)-insulin pentamethyl ester was purified. This compound was digested by carboxypeptidase B to remove the arginine residue B22 at the end of the B chain. Then the N-terminal amino groups of the remaining desnonapeptide-(B22 - 30)-insulin pentamethyl ester were protected with the Boc residue. The free carboxyl group of the glutamic acid residue B21 of this product was coupled to the following synthetic tetrapeptide esters: Arg-Gly-Phe-Phe-OMe, Lys(Boc)-Gly-Phe-Phe-OMe, Orn(Boc)-Gly-Phe-Phe-OMe, Cit-Gly-Phe-Phe-OMe, Ala-Gly-Phe-Phe-OMe and Gly-Gly-Phe-Phe-OMe. The syntheses of these peptide esters are described. After removal of all protecting groups, despentapeptide-insulin (B22-Arg) and analogues of this product with variation in position B22 could be obtained. They were purified by column chromatography. The biological activities of these components were determined by the mouse fall test. In the case of despentapeptide insulin (C-terminus Arg-Gly-Phe-Phe), the activity rose to the expected value of 34%. The insulin variants with amino acid residues other than arginine in position B22 had much lower activities: with lysine 13%, with ornithine 12%, with citrulline 9%, with alanine 8% and with glycine 6%. Desnonapeptide-insulin by itself posses an activity of 3%. These results demonstrate once more the essential nature of arginine residue B22 for insulin activity.

Animals↗
PubMed2003

Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: a randomized controlled trial.

Insulin, insulin-like growth factors (IGFs) I and II, and IGF binding proteins (IGFBPs) 1 and 3 have been implicated in breast cancer outcomes. We conducted a randomized controlled trial to determine the physiological effects of exercise training on changes in these biological markers in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control group (n = 28). The exercise group trained on cycle ergometers three times per week for 15 weeks. The control group did not train. End points included changes in fasting insulin, glucose, insulin resistance, IGF-I, IGF-II, IGFBP-1, IGFBP-3, and IGF-I:IGFBP-3 molar ratio between baseline and week 15. All of the statistical tests were two-sided (alpha = 0.05). Fifty-two participants completed the trial. The exercise group completed 44.3 of 45 (98.4%) prescribed exercise sessions. Baseline hormone concentrations did not differ between groups except that IGF-II was higher in the exercise group (P = 0.011). No significant differences between groups were observed for changes in fasting insulin (+6.3 pmol/liter; P = 0.941), glucose (+0.09 mmol/liter; P = 0.824), insulin resistance (+0.4; P = 0.247), IGF-II (-40.7 ng/ml; P = 0.101), or IGFBP-1 (+1.4 ng/ml; P = 0.774). However, significant differences between groups were observed for changes in IGF-I (-7.4 ng/ml; P = 0.045), IGFBP-3 (+180.5 ng/ml; P = 0.021), and IGF-I:IGFBP-3 molar ratio (-0.006; P = 0.017). Exercise training had significant physiological effects on IGF-I, IGFBP-3, and IGF-I:IGFBP-3 molar ratio in postmenopausal breast cancer survivors. The clinical implications of these findings remain to be defined.

Aged↗
PubMed1997

Increased circulating leptin concentrations in insulin-resistant first-degree relatives of patients with non-insulin-dependent diabetes mellitus: relationship to body composition and insulin sensitivity but not to family history of non-insulin-dependent diabetes mellitus.

OBJECTIVE: To explore a possible association between serum concentration of leptin, insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: Forty first-degree relatives of NIDDM patients and 35 control subjects matched for age, gender and body mass index underwent a hyperinsulinaemic (insulin infusion rate 0.6 mU/kg per min) euglycaemic clamp combined with indirect calorimetry. Serum leptin was measured in fasting blood samples obtained before the clamp. RESULTS: All subjects had a normal oral glucose tolerance test. Insulin-stimulated glucose uptake (M) was decreased in the relatives compared with the control subjects (4.58 +/- 0.27 versus 6.06 +/- 0.25 mg/kg per min, P < 0.001). Conversely, serum leptin was increased in the relatives (9.6 x/divided by 1.1 versus 6.1 x/divided by 1.2 ng/ml (geometric mean x/divided by antilog S.E.M.), P < 0.05). A positive correlation was observed between circulating levels of leptin and percentage body fat (P < 0.001) and inverse correlations were found between leptin, M (P < 0.01), maximal aerobic capacity (VO2 max) (P < 0.01), and energy expenditure (P < or = 0.01) in both groups. In multiple linear regression analysis, percentage body fat, gender and M significantly determined the level of leptin (r2 = 0.71, P < 0.001) whereas family history of NIDDM and VO2 max did not. CONCLUSION: Serum leptin is increased in insulin-resistant offspring of NIDDM patients. The association between leptin, anthropometric measures and insulin sensitivity is, however, comparable with that of a control group. The increased concentrations of serum leptin in the relatives appear to be associated with the insulin resistance, but not with a family history of NIDDM.

Administration, Oral↗
PubMedDate not supplied

Prolonged fasting hypoglycemia due to insulin antibodies in patient with non-insulin-dependent diabetes mellitus: effect of insulin withdrawal on insulin-antibody-binding kinetics.

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped, occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18-25 microU/ml) and extremely high antibody-bound insulin (greater than 20,000 microU/ml) but normal counter-regulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over 13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.

Aged↗
PubMed1995

Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance.

We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandial triglyceride (TG)-rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:cholesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intestinal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a preponderance of small dense LDL particles present in the plasma and reduced amounts of large buoyant species when compared to normotriglyceridaemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concentrations of proinsulin (P < 0.05), although insulin content did not differ significantly. 32-33 split proinsulin (SPI) was the major insulin-like molecule present in HTG and was present in significantly higher amounts in these patients (P < 0.05) than either NTG or control subjects and correlated significantly with the presence of small dense LDL particles. After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylomicron remnants were present to a greater extent in HTG than in NTG and controls (P < 0.05), although in this case NTG also contained more chylomicron remnants than control subjects (P < 0.05). There was no difference in the LPL activity, CETP and LCAT between diabetics and controls, whereas an increase in hepatic lipase activity was seen in the HTG diabetics (P < 0.05). Both CETP and LCAT activities increased postprandially. Multivariate analysis showed that TG, HDL content and HL activity were the most important determinants of small dense LDL concentration in the fasting state (R2 = 67%). Postprandially, chylomicron remnant clearance, HL and insulin resistance were the major determinants (R2 = 61%) of LDL-III.

Case-Control Studies↗
PubMed1998

Effects of a short-acting insulin analog (Insulin Lispro) versus regular insulin on lipid metabolism in insulin-dependent diabetes mellitus.

Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the physiological postprandial insulin profile. The aim of this study was to compare the effects of intensive insulin therapy on lipid metabolism using preprandial IL and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM) subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did not change after both treatments. In IDDM patients, total cholesterol and triglyceride levels appeared lower after RI than after IL. The low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P < .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities were observed at baseline, the protein content was lower (P < .05) after IL (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05). LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both treatments and did not normalize. IDDM and control subjects showed similar LDL subfraction distribution at baseline and after both treatments. Two-hour postprandial VLDL composition alterations, although improved after RI, completely normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) activities were similar to the control group and did not change after both treatments. Hepatic lipase (HL) activity was lower in diabetic patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after both treatments. In conclusion, in IDDM patients, IL (injected immediately before the meal) may offer small different effects on lipoprotein metabolism versus RI (injected 30 minutes before the meal) that, taken together, do not seem relevant.

Adult↗
PubMed1981

Effect of trypsin treatment of rat adipocytes on biological effects and binding of insulin and insulin-like growth factors: further evidence for the action of insulin-like growth factors through the insulin receptor.

Trypsin-treatment of isolated rat adipocytes abolishes the metabolic effects not only of insulin, but also of the insulin-like growth factors: in trypsin-treated cells, concentrations of these hormones that are otherwise maximally effective no longer stimulate 3-O-methylglucose transport and lipogenesis or inhibit epinephrine induced lipolysis. Concomitantly, the trypsin-treated adipocytes no longer display specific insulin binding. In contrast, the characteristics of the binding of the insulin-like growth factors are not grossly affected by prior trypsinization of the adipocytes. These findings add further support to the concept that the insulin-like growth factors act on glucose metabolism and antilipolysis via the insulin receptor of the adipocyte.

3-O-Methylglucose↗