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At least 19 recordsLinked to original sources
PubMed1984

Enhanced efficacy of U-500 insulin in the treatment of insulin resistance caused by target tissue insensitivity.

This report describes a 55-year-old diabetic patient with severe insulin resistance due to obesity and hepatic cirrhosis. Anti-insulin antibodies were responsible for only a minor part of the insulin resistance. Insulin resistance was mediated primarily at the target tissue level by a combination of insulin receptor deficiency and a postreceptor defect. When the patient was treated with U-500 regular pork insulin subcutaneously, her insulin requirement was only one third to one half of that during U-100 NPH or regular insulin treatment. The reasons for the greater efficacy of U-500 insulin are unknown. U-500 insulin may have a place in the optimization of therapy for patients with insulin resistance of nonimmunologic origin.

Diabetes Mellitus↗
PubMed1981

U-500 insulin in the treatment of antibody-mediated insulin resistance.

Three patients with antibody-mediated insulin resistance were treated with U-500 regular insulin subcutaneously. Insulin requirements decreased dramatically (55% to 75%) when therapy was changed from U-100 NPH pork to equivalent doses of U-500 regular pork insulin. There was no difference in antibody affinity for the insulin in these two preparations as shown by competition experiments. These observations demonstrate that U-500 insulin is a useful alternative in the treatment of antibody-mediated insulin resistance. The mechanism for this effect is yet to be determined.

Adult↗
PubMed1998

Time to peak insulin level, relative bioavailability, and effect of site of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus.

Seven fasting patients with noninsulin-dependent diabetes mellitus (NIDDM) inhaled 1.0 U/kg of body weight of nebulized regular pork insulin by mouth or were subcutaneously (sc) injected with 0.1 U/kg of body weight of insulin in the upper arm on two different occasions. The time to peak insulin level was compared for the two treatment modalities. Insulin bioavailability after inhalation was quantified relative to sc injected insulin. Deposition of a radiolabeled insulin surrogate aerosol (insulin diluent) in the larger central airways versus the peripheral airways, expressed as the inner-to-outer (I:O) ratio, and in the lung apex versus the lung base, expressed as the apex-to-basal (A:B) ratio, was quantified with gamma scintigraphy. Ratios were related to glucose responses after inhalation of insulin. Times to peak insulin level were similar for the two methods of treatment, averaging 43 +/- 16 and 64 +/- 40 minutes after inhalation and sc injection of insulin, respectively. The bioavailability of inhaled insulin averaged 14.7% +/- 5.8% relative to sc injected insulin. This was significantly less than the average bioavailability of deposited drug (18.9% +/- 5.3%) relative to sc injected insulin (P < 0.05). I:O and A:B ratios for the surrogate aerosol averaged 1.3 +/- 0.4 and 0.7 +/- 0.2, respectively. Linear regression analysis revealed that the maximum percentage of decrease in glucose after insulin inhalation was significantly related to the A:B ratio such that percentage decrease in glucose was greater in patients who demonstrated a lower A:B ratio (P = 0.003). Percentage decrease in glucose was not related to the I:O ratio. These results indicate that the bioavailability of nebulized insulin inhaled by mouth is approximately 20% when calculated in terms of drug deposited and suggest that increasing the distribution of insulin aerosol to the base of the lung enhances the glucose response in patients with NIDDM during the fasting state.

Administration, Inhalation↗
PubMed1995

DS-1, a modified Quillaja saponin, enhances ocular and nasal absorption of insulin.

The purpose of this study was to test DS-1, a modified Quillaja saponin, for its efficacy as an absorption enhancer. Anesthetized rats receiving eyedrops or nosedrops formulated with regular pork insulin in saline showed no hypoglycemic response, indicating no systemic absorption of insulin. However, rats receiving eyedrops or nosedrops formulated with insulin plus 0.025-0.10% DS-1 showed rapid absorption of insulin and a concomitant decrease in serum D-glucose levels. No response was observed following sublingual or buccal delivery of insulin. In conclusion, the modified saponin DS-1 was efficacious at enhancing nasal or ocular insulin delivery at extremely low concentrations. The mechanism of DS-1 action is not yet known.

Absorption↗
PubMed1979

A case of maturity-onset diabetes mellitus resistant to insulin but responsive to tolbutamide.

A nonobese patient with maturity-onset diabetes mellitus was hospitalized for treatment of an ulcer on his right foot. During this episode, his diabetic control worsened, and he proved unresponsive to exogenous insulin. Unresponsiveness to insulin persisted after healing of the ulcer. Tolbutamide therapy was then begun and produced a marked reduction in blood sugar levels. Withdrawal of the drug was accompanied by a progressive rise in blood sugar level. Intravenous infusion of regular pork insulin at rates of 45 U/h and single-component pork insulin at rates of 120 U/h had minimal effect on the blood sugar level. High levels of antibody to beef insulin were measured, with lower levels of pork insulin antibodies. C-peptide values were in a normal range before tolbutamide treatment and increased after use of the drug.

Administration, Oral↗
PubMed1977

Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man.

To investigate the role of glucagon in regulating hepatic glucose production in man, selective glucagon deficiency was produced in four normal men by infusing somatostatin (0.9 mg/h) and regular pork insulin (150-muU/kg per min) for 2 h. Exogenous glucose was infused to maintain euglycemia. Arterial plasma glucagon levels fell by greater than 50% whereas plasma insulin levels were maintained in the range of 10-14 muU/ml. In response to these hormonal changes, net splanchnic glucose production (NSGP) fell by 75% and remained suppressed for the duration of the study. In contrast, when somatostatin alone was administered to normal men, resulting in combined insulin and glucagon deficiency (euglycemia again maintained), NSGP fell markedly but only transiently, reaching its nadir at 15 min. Thereafter, NSGP rose progressively, reaching the basal rate at 105 min. These data indicate that the induction of selective glucagon deficiency in man (with basal insulin levels maintained) is associated with a marked and sustained fall in hepatic glucose production. We conclude, therefore, that basal glucagon plays an important role in the maintenance of basal hepatic glucose production in normal man.

Adolescent↗
PubMed1987

Biosynthetic human insulin improves postprandial glucose excursions in type I diabetics.

To determine if the more rapid absorption of subcutaneously administered human insulin, as compared with animal insulin, would result in an improved postprandial metabolic response, ten persons with type I diabetes mellitus were studied during a fixed meal. Plasma glucose and insulin concentrations were compared after subcutaneous injections of 0.2 U/kg body weight of regular biosynthetic human insulin or regular purified pork insulin in a double-blind randomized crossover trial. Meal glycemic excursions improved after the administration of biosynthetic human insulin, when compared with purified pork insulin (p less than 0.05 at 150, 180, and 210 minutes postprandially). Serum free immunoreactive insulin concentrations were significantly higher after injections of biosynthetic human insulin, and the rate of incremental rise during the first 30 minutes was also greater. Insulin antibody studies showed a strong negative correlation between peak insulin levels and the association constant for the high-affinity-binding insulin antibodies. We conclude that biosynthetic human insulin is more rapidly absorbed after subcutaneous injection than is purified pork insulin, a characteristic that results in improved postprandial metabolic control.

Absorption↗
PubMed1992

In vivo proliferation of rat vascular smooth muscle in relation to diabetes mellitus insulin-like growth factor I and insulin.

The roles of diabetes mellitus, insulin-like growth factor I and insulin in vascular smooth muscle proliferation in vivo were studied. Proliferation was induced by endothelial injury (balloon catheterization) of rat aorta, and was measured as 3H-thymidine incorporation into DNA. Levels of insulin-like growth factor I mRNA and insulin-like growth factor I receptor mRNA were measured with a solution hybridization assay. The increase in DNA synthesis was most pronounced 2 days after injury in both normal and diabetic rats and declined thereafter, but DNA synthesis in aortas from diabetic rats was lower throughout the time period studied. Levels of insulin-like growth factor I mRNA and the receptor mRNA were both increased in balloon catheterized aortas, and time-course studies showed an increase in receptor mRNA prior to the increase in insulin-like growth factor I mRNA. Diabetic rats were treated with equimolar concentrations of insulin (35 nmol/day) or insulin-like growth factor I (31 nmol/day) for 5 days. Insulin-like growth factor I increased DNA synthesis in injured aortas 2 days after injury without improving blood glucose, whereas the effect of insulin was associated with a decrease in blood glucose levels. In conclusion, vascular smooth muscle proliferation is impaired by diabetes and stimulated by insulin treatment. Insulin-like growth factor I infusion stimulates vascular smooth muscle proliferation without affecting blood glucose, and gene expressions of insulin-like growth factor I and its receptor are increased in proliferating vascular smooth muscle, indicating that insulin-like growth factor I and involved in vascular smooth muscle proliferation in vivo.

Animals↗
PubMed2002

Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1.

Insulin and insulin-like growth factor-1 (IGF-1) act through highly homologous receptors that engage similar intracellular signaling pathways, yet these hormones serve largely distinct physiological roles in the control of metabolism and growth, respectively. In an attempt to uncover the molecular mechanisms underlying their divergent functions, we compared insulin receptor (IR) and IGF-1 receptor (IGF-1R) regulation of gene expression by microarray analysis, using 3T3-L1 cells expressing either TrkC/IR or TrkC/IGF-1R chimeric receptors to ensure the highly selective activation of each receptor tyrosine kinase. Following stimulation of the chimeric receptors for 4 h, we detected 11 genes to be differentially regulated, of which 10 were up-regulated to a greater extent by the IGF-1R. These included genes involved in adhesion, transcription, transport, and proliferation. The expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen, was markedly increased by IGF-1R but not IR activation. This effect was dependent on MAPK, but not phosphatidylinositol 3-kinase, and did not require an autocrine loop through the epidermal growth factor receptor. HB-EGF mitogenic activity was detectable in the medium of 3T3-L1 preadipocytes expressing activated IGF-1R but not IR, indicating that the transcriptional response is accompanied by a parallel increase in mature HB-EGF protein. The differential abilities of the IR and IGF-1R tyrosine kinases to stimulate the synthesis and release of a growth factor may provide, at least in part, an explanation for the greater role of the IGF-1R in the control of cellular proliferation.

3T3 Cells↗
PubMedDate not supplied

The plasma glucose response of normal fasting subjects to neutral regular and NPH biosynthetic human and purified pork insulins.

Using doses of 0.1 and 0.15 U/kg, the hypoglycemic activities of neutral regular and NPH biosynthetic human insulin (BHI) and purified pork insulin were compared in normal fasting subjects. Neutral regular insulin was administered by the intravenous and subcutaneous routes and NPH subcutaneously. Comparison of the plasma glucose curves disclosed no statistically significant differences between the maximum effects and the length of time to achieve the maximum effect. Moreover, a dose-response difference between 0.1 and 0.15 U/kg could not established. It is concluded that the hypoglycemic activities of neutral regular and NPH BHI and purified pork insulin are the same.

Animals↗