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Biomedical subjects

A E Kitabchi

Publications and source records attributed to A E Kitabchi.

At least 73 records · Page 4Linked to original sources
PubMed1982

Hypercortisolism and insulin resistance: comparative effects of prednisone, hydrocortisone, and dexamethasone on insulin binding of human erythrocytes.

We have studied the effects of 3 days of hydrocortisone (30 mg every 8 h), dexamethasone (1 mg every 8 h), and prednisone (7.5 mg every 8 h) ingestion on glucose intolerance and insulin resistance in three groups of lean normal volunteers and compared these parameters to specific insulin binding in erythrocytes. All three glucocorticoids caused significant reduction of glucose tolerance as assessed by glucose and insulin areas under oral glucose tolerance text curves and insulin sensitivity in response to 0.1 U insulin/kg BW, iv. Although both hydrocortisone and dexamethasone caused significant reduction in insulin binding compared to that during the pretreatment period (11.0 +/- 0.7 vs. 9.0 +/- 0.5% (P less than 0.01) and 11.8 +/- 0.7 vs. 9.0 +/- 0.5% (P less than 0.05), respectively), prednisone ingestion did not significantly alter insulin binding (10.6 +/- 0.6 before vs. 9.4 +/- 0.5% after). Decreased insulin binding with hydrocortisone and dexamethasone was caused by decreased binding affinity rather than by a decreased number of receptors. In two subjects in whom receptor binding was measured daily for 3 days during prednisone (one subject) or hydrocortisone (one subject) ingestion, the inhibition of binding was highest on the first day, with subsequent reduction of this inhibited binding toward normal by the third day. We conclude that although hydrocortisone, dexamethasone, and prednisone all cause deterioration of glucose tolerance and decreased insulin sensitivity, only hydrocortisone and dexamethasone exhibit significant decreases in insulin binding to erythrocytes. This decreased binding is not due to changes in receptor numbers but to decreased affinity brought about by hyperinsulinemia. Prednisone ingestion caused significant insulin resistance with an insignificant decrease in insulin binding. We believe that other mechanisms, such as alteration of postreceptor events, may play a major role in the induction of insulin resistance in hypercortisolism in man.

Adult↗
PubMed1982

A rapid means of separating A14-125I-insulin from heterogeneously labeled insulin molecules for biologic studies.

We have used two methods for the preparation of a highly homogeneous insulin with high specific activity. After iodination with chloramine T, the labeled peptides were retained on a disposable Sep Pak cartridge and subsequently eluted. The eluted labeled insulins were further purified by either DEAE cellulose or high performance liquid chromatography (HPLC) to separate A14-125I- from A19-125I-insulin. Both methods of chromatography were effective, but HPLC offered the advantage of better resolution in less time and higher yields of A14-125I-insulin, which is suitable for biologic studies in various target tissues.

Chromatography, High Pressure Liquid↗
PubMed1982

Effects of insulin on plasma lipoproteins in diabetic ketoacidosis: evidence for a change in high density lipoprotein composition during treatment.

To determine the acute effects of insulin on lipoprotein metabolism, we have followed the plasma lipoprotein lipid and apolipoprotein levels during insulin therapy for the first 24 hr in 13 patients with diabetic ketoacidosis. Corrections were made for plasma volume changes during treatment. Before insulin treatment, mean plasma triglyceride and cholesterol levels were 574 mg/dl (range 53-2355) and 212 mg/dl (range 118-416), respectively. Insulin therapy resulted in rapid decreases in triglyceride-rich lipoproteins, chylomicrons, and very low density lipoproteins (VLDL), with most patients achieving plasma triglyceride levels below 150 mg/dl at 24 hr. Mean basal levels of intermediate density lipoproteins (IDL) and low density lipoproteins (LDL)-cholesterol were low (9.9 and 72 mg/dl, respectively) and were statistically invariant with therapy. Mean basal levels of high density lipoprotein (HDL) cholesterol were also low (26 mg/dl, range 5-48) and were invariant during the first 12 hr and increased significantly to 29 mg/dl by the 24th hr. Plasma apoprotein (apo) B levels were in the upper normal range (101 mg/dl) before treatment and decreased with therapy due to significant decreases in VLDL, but not IDL or LDL apoB. VLDL appeared to have a normal apoprotein composition which did not change with treatment. Mean apoA-I levels which were near normal in plasma and HDL before therapy, decreased significantly (16%) by 12 hr and subsequently increased towards basal levels between 12 and 24 hr. The ratio of apoA-I to cholesterol in HDL also fell significantly during the entire 24 hr. Density gradient ultracentrifugal analysis of the d > 1.006 g/ml fractions indicated a selective decrease in "lighter" density fractions of HDL-apoA-I during treatment. These results provide evidence that insulin may decrease the secretion of apoA-I into plasma or increase catabolism.-Weidman, S. W., J. B. Ragland, J. N. Fisher, Jr., A. E. Kitabchi, and S. M. Sabesin. Effects of insulin on plasma lipoproteins in diabetic ketoacidosis: evidence for a change in high density lipoprotein composition composition during treatment.

Adolescent↗
PubMed1981

Reversible hyperinsulinuria in diabetic ketoacidosis in man.

Urinary clearance and fractional urinary clearance of immunoreactive insulin (IRI) and beta 2-microglobulin (I beta 2M) were studied in patients with diabetic ketoacidosis (DKA) before, during, and after treatment. Our results indicate that in DKA in man a) there is an approximate 250-fold increase in urinary and fractional urinary clearance of IRI and a 600-fold increase in urinary and fractional urinary I beta 2M clearance, which suggests that the hyperinsulinuria is secondary to a nonspecific defect in tubular luminal uptake of low-molecular-weight proteins, although decreased IRI degradation cannot be excluded; b) because increased IRI clearance is not changed by the pharmacologic plasma IRI levels achieved, the residual tubular absorptive capacity is not saturable; c) I beta 2M clearance but not IRI clearance is significantly improved by the time metabolic control is attained, suggesting separate tubular transport systems; d) a small, therapeutically insignificant fraction of the infused insulin is lost in the urine during therapy of DKA; and e) defective renal tubular luminal uptake (and possibly degradation) of IRI is reversible.

Adolescent↗
PubMed1981

Glucose intolerance and insulin resistance in aplastic anemia treated with oxymetholone.

Because of a suspected association between the drug oxymetholone and abnormal glucose metabolism, we determined immunoreactive insulin (IRI) and plasma glucose during oral glucose tolerance testing in seven patients with aplastic anemia, six of whom received oxymetholone therapy. All patients receiving oxymetholone therapy had abnormal glucose and/or IRI values. This finding was independent of GH, cortisol, and glucagon. In one patient, glucose and IRI levels were normal before oxymetholone but became abnormally elevated after the use of this drug. Furthermore, normal glucose and IRI values were present in the single patient not receiving oxymetholone. Thus, a positive relationship was demonstrated between oxymetholone administration and the presence of glucose intolerance and insulin resistance.

Adolescent↗
PubMed1981

Correlation between plasma and urine glucose in diabetes.

To determine whether semiquantitative glucose measurements of spot urine specimens accurately reflect prevailing plasma glucose levels, we compared reported levels from 400 second-voided urines to simultaneous plasma determinations from 246 adult diabetics. Quantitative urine levels and plasma glucose levels correlated. However, when semiquantitative urinary determinations were compared to plasma glucose stratified into 0 to 149, 150 to 199, and greater than 200 mg/dL, 75% of the urine samples associated with plasma levels from 150 to 199 mg/dL were negative by Diastix, and 16.5% of samples negative by Diastix were in the 200+ mg/dL plasma range. Only 9% of samples from 0 to 149 mg/dL showed any positive Diastix readings. Because of the low sensitivity of semiquantitative methods, we fell that, except for detection of marked hyperglycemia, spot urine glucose determinations are inadequate as the sole means of clinical assessment for management of diabetic patients. Home glucose monitoring may be a better alternative for follow-up of these patients.

Adult↗
PubMed1980

Low-dose insulin for treatment of diabetic ketoacidosis in a private community hospital.

We evaluated 21 patients with the diagnosis of diabetic ketoacidosis, involving 25 admissions to a large private community hospital, to evaluate the efficacy of low-dose insulin therapy by measuring time required for correction of hyperglycemia and acidosis, and to evaluate any associated morbidity or mortality. The protocols and laboratory tests were relatively loose and less stringent than our previous protocols, to permit flexibility of therapy by various physicians and to simulate the prevailing practice in such a hospital. All patients responded with correction of hyperglycemia within nine hours and acidosis within 12 hours, with averages of 5.61 and 6.8 hours, respectively. No deaths were recorded in the group. From these data, it is apparent that the low-dose insulin regimen is a safe, effective, and practical method for therapy of DKA in the private community hospital.

Adult↗
PubMed1980

Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease.

We evaluated basal plasma total immunoreactive insulin (insulin), androstenedione, and testosterone in 14 obese women: 8 with polycystic ovarian disease (PCOD) and 6 obese controls. All 3 hormones were significantly elevated (P less than 0.02 to P less than 0.001) in PCOD patients. A significant correlation among basal levels of plasma insulin, androstenedione, and testosterone was demonstrated. The PCOD group had significantly higher levels of glucose at 1, 2, and 3 h, with similar significant increases in plasma insulin levels at 0, 2, and 3 h. A significant correlation was found between plasma insulin response areas and plasma testosterone (P less than 0.001) in the control and PCOD patients. These studies demonstrate that hyperandrogenism correlates with hyperinsulinism.

Adolescent↗
PubMed1980

beta-Endorphin and beta-lipotropin plasma levels in hirsute women: correlation with body weight.

Based on the findings of elevated circulating beta-endorphin (beta-END) levels in genetically obese (fa/fa) fats and the reversal of the overeating of genetically obese (ob/ob) mice by naloxone, circulating beta-END and beta-lipotropin (beta-LPH) levels were measured in 8 hirsute, hyperandrogenic, oligo-amenorrheic women of varying weights. Circulating beta-END and beta-LPH levels were significantly elevated (p less than .001) above the levels in nonobese control subjects and were positively correlated with body weight (p less than .025). Based on these data and indirect evidence in the literature, we propose a role may exist for beta-END and/or beta-LPH in human obesity and in adrenal androgen secretion.

Adolescent↗
PubMed1980

Decreased insulin binding of human erythrocytes after dexamethasone or prednisone ingestion.

We have investigated changes in insulin binding in erythrocytes in response to overnight ingestion of 1 mg dexamethasone or 10 mg of prednisone in two groups of eight lean, healthy subjects. Dexamethasone administration reduced insulin binding from 9.6 to 6.8% (P < 0.001) with concomitant increase in basal plasma insulin from 10.5 to 14.1 microU/ml (P < 0.05). Prednisone ingestion reduced insulin binding from 9.9 to 7.9% (P < 0.01), but the increase in basal insulin from 16.9 to 20.6 microU/ml was not significantly different. The decrease in insulin binding with both dexamethasone and prednisone was associated with decreased affinity of erythrocyte for insulin at low occupancy and the increase in the dose of unlabeled insulin resulted in 50% inhibition of specific binding without changes in the number of receptors. The earliest decrease in insulin binding was noted within 2 h after ingestion of 1 mg of dexamethasone. These data suggest that acute alteration of insulin receptor function could occur in erythrocytes by small amounts of dexamethasone or prednisone through a mechanism consistent with a decrease in receptor affinity rather than a decrease in the number of receptors.

Adult↗
PubMed1979

Initial site of insulin cleavage by insulin protease.

Exposure of insulin to insulin protease (insulinase, EC 3.4.22.11), a degradative enzyme with considerable specificity toward insulin, results in alterations in the properties of the insulin molecule. Limited degradation by the enzyme results in a decrease in the ability of insulin to bind to membrane receptors with less change in the immunoprecipitability or trichloracetic acid precipitability of the hormone. Limited degradation by insulin protease also alters insulin so that the molecule becomes susceptible to attack by nonspecific endopeptidases which have no effect on unaltered insulin. These data demonstrate the production of an intermediate in the proteolytic degradation of insulin. By labeling with [14C]dansyl chloride, an insulin intermediate with three amino-terminal residues, glycine, phenylalanine, and leucine, was identified. Analysis of this intermediate demonstrated that it was composed of an intact A chain and a B chain cleaved between residues B16 and B17, with the three peptide chains held together by disulfide bonds. Based on these findings, we hypothesize that a stepwise degradation of insulin occurs in vivo and that an early step in the process is the cleavage between B16 and B17 that renders the molecule sucseptible to further degradation by nonspecific proteases.

Amino Acid Sequence↗
PubMed1979

The effect of age on insulin-degrading activity in rat tissue.

Insulin-degrading activity was measured in the 100,000g supernatant fraction of muscle, liver, and kidney from rats of varying ages. Young animals (four weeks old) had the highest activity in all three tissues. By seven weeks of age the activity in both muscle and liver had decreased significantly as compared with four-week-old animals. A slight but nonsignificant decrease occurred in kidney. In animals over one year of age the insulin-degrading activity in all three tissues was significantly less than the activities at either four or seven weeks. In contrast the effect of age on degradation of albumin and parathormone was much less marked.

Aging↗
PubMed1979

Insulin binding and degradation by muscles from streptozotocin-diabetic rats.

Insulin degradtion by muscle was examined in normal, streptozotocin-induced diabetic rats, and diabetic rats treated with insulin. Insulin degradation by the 100,000 X g supernatant fractions was identical in all three groups, but insulin metabolism by the intact epitrochlaris muscle was significantly increased in diabetic animals. Insulin treatment of the diabetic animals partially restored the activity toward normal. Specific binding of 125l-insulin to the intact muscles was also increased in the diabetic animals. Streptozotocin diabetes, therefore, increased the binding and degradation of insulin by intact muscle but did not alter the insulin degradation by the total soluble intracellular degradative activity.

Animals↗