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Biomedical subjects

A E Kitabchi

Publications and source records attributed to A E Kitabchi.

At least 91 records · Page 5Linked to original sources
PubMed1979

Similar responsiveness of diabetic ketoacidosis to low-dose insulin by intramuscular injection and albumin-free infusion.

We compared low-dose insulin regimens in a prospective randomized trial in 30 patients with diabetic ketoacidosis. One group received a loading dose of 0.44 U/kg body weight of regular insulin half intramuscularly and half intravenously followed by 7 U/h intramuscularly, whereas the other group received a loading dose of 0.44 U/kg intravenously followed immediately by a constant infusion of 7 U/h in albumin-free saline. The time for metabolic control of the ketoacidosis was not significantly different in the two groups. Five patients in each group developed mild hypokalemia (serum potassium, 3.0 to 3.4 meq/litre). No patient became hypoglycemic, and there were no deaths within the follow-up period (24 h). In the treatment of diabetic ketoacidosis, low doses of insulin administered by the priming dose-intermittent intramuscular route are as effective as the constant infusion method.

Adult↗
PubMed1978

Dipivalyl epinephrine: a new pro-drug in the treatment of glaucoma.

The dansyl chloride technique in conjunction with thin layer chromatography and autoradiography has shown that dipivalyl epinephrine is a pro-drug in the human eye. Dipivalyl epinephrine appears to be a more effective epinephrine compound, in that it penetrates the cornea approximately 17 times greater than epinephrine.

Aqueous Humor↗
PubMed1978

Factors influencing the handling of insulin by the isolated rat kidney.

The renal handling of immunoreactive insulin was studied in the isolated perfused normothermic rat kidney to determine (a) the relative contributions of glomerular clearance and peritubular clearance to the renal clearance of insulin under different conditions, (b) what metabolic factors influence the ability of tubular cells to remove insulin from the glomerular filtrate and the peritubular circulation, and (c) whether the same factors influence the luminal and contraluminal uptake of insulin.In control kidneys the organ clearance of insulin (OCi) was 974+/-63 mul/min (SEM), of which a maximum of 46% could theoretically be accounted for by filtration. OCi was not altered by fasting, lack of exogenous fuel (glucose), or the addition of cyanide. The glomerular filtration rate did not correlate with the OCi, but there was a significant (P < 0.001) negative correlation (r = -0.828) between the peritubular clearance and glomerular filtration rate. Both N-ethylmaleimide and cold (10 degrees C) reduced the rate of insulin removal. Fractional excretion of filtered insulin (9.7+/-1.7% in controls) was not significantly altered by fasting or perfusing without glucose. In contrast, KCN increased fractional excretion of insulin to 41.9+/-3.7% whereas cold increased fractional excretion to 69.0+/-3.3%. This study indicates that renal tubular cells remove insulin from the tubular lumen and the peritubular compartment. Furthermore, the data suggest that insulin removal by tubular cells is a temperature-sensitive process consisting of two different systems. The system associated with the luminal aspect of the cell appears to be dependent on oxidative metabolism, whereas the system associated with the contraluminal aspects of the cell appears to be independent thereof. Under several circumstances when the glomerular clearance of insulin falls thereby reducing the amount of insulin absorbed by the luminal aspect of the cell, contraluminal uptake increases, and a constant rate of insulin removal is maintained by the kidney.

Animals↗
PubMed1977

Diabetic ketoacidosis: low-dose insulin therapy by various routes.

Since in normal persons the hypoglycemic effect of low-dose intramuscular exceeds that of subcutaneous insulin we studied the effect of routes of insulin therapy in diabetic ketoacidosis. Forty-five patients with diabetic ketoacidosis entered a randomized prospective protocol with insulin administered either intravenously, subcutaneously or intramuscularly. Initial priming dose of insulin had to be repeated in two of 15, three of 15 and six of 15 of the intravenous, subcutaneous and intramuscular groups respectively. The intravenous group had a more rapid fall in plasma glucose (P less than 0.01) and ketone bodies (P less than 0.05) during the first two hours. Thereafter, there were no significant differences in the rate of decline of plasma glucose or ketones nor in the time required for glucose to reach 250 mg per deciliter or for complete recovery from diabetic ketoacidosis. The data confirm the efficacy of low-dose insulin therapy for diabetic ketoacidosis and indicate that the optimal route of insulin administration is by initial intravenous combined with subcutaneous or intramuscular.

Adult↗
PubMed1977

Proinsulin and C-peptide: a review.

The recent work on proinsulin and C-peptide has been reviewed with major emphasis on the most significant findings since 1972. Proinsulin has now been established as the biosynthetic precursor of insulin in all species examined, including man, with a preproinsulin as a possible precursor of the prohormone. The conversion of proinsulin which appears to occur exclusively in the pancreas leads to equimolar production of insulin and C-peptide. Although proinsulin has a direct biologic effect which is one-tenth as much as that of insulin, C-peptide has no biologic activity on homologous or heterologous tissue and no ability to modify the action of insulin and/or proinsulin. Previous work on proinsulin immunoassay suggested that this prohormone, but not C-peptide, cross-reacts with insulin antiserum. On the other hand, in the C-peptide immunoassay, proinsulin but not insulin cross-reacts with the antiserum. Up to this time, therefore, it has not been possible to immunoassay human proinsulin or C-peptide specifically. The very recent work from the laboratory of Heding, however, has brought about major advances in this area in which human C-peptide and proinsulin can be separated in the plasma by the use of Sepharose particles. With this recent major advancement, it is now possible to measure human C-peptide specifically. This measurement has been shown to be a useful tool for the assessment of beta-cell function in diabetic patients treated with insulin and in insulinoma patients in whom endogenous C-peptide secretion is not suppressed with exogenous insulin-induced hypoglycemia. With the use of a specific enzyme which degrades insulin but not proinsulin, postprandial plasma proinsulin values have been measured in a large number of subjects under a variety of physiologic and pathologic conditions. These results, which are comparable to those obtained by the more laborious column chromatography, could be summarized as follows: (1) proinsulin values in lean, young normal subjects do not vary greatly in response to insulin secretagogues; (2) proinsulin secretion in response to glucose results in a greater percentage of proinsulin in the older age group than in the younger group; (3) in lean adult and juvenile diabetic patients, the percentage of proinsulin is not excessive, whereas obese diabetics and pregnant diabetics appear to secrete relatively greater proinsulin than their diabetic controls; and (4) whereas most hyperinsulinemic states (Cusing's syndrome, adult-onset diabetics, acromegaly, and glucocorticoid therapy) are not associated with an increase in percentage of proinsulin, hyperinsulinemia of insulinoma, selected cases of functional hypoglycemia, and genetic hyperproinsulinemia are associated with a greater percentage of proinsulin. Identification of a possible new proinsulin intermediate(s) in these conditions deserves further investigation...

Amino Acid Sequence↗
PubMed1976

Insulin and proinsulin in normal and chemical diabetic children.

Plasma levels of total immunoreactive insulin and immunoreactive proinsulin were studied in 10 normal children and 15 children with chemical diabetes ranging in age from 5 to 13 years. Eleven of the children with chemical diabetes demonstrated significantly elevated TIRI during fasting and following glucose administration. There was a delay in the increment of plasma TIRI in four children with chemical diabetes, but otherwise their TIRI levels were normal. In these four children IRP was not significantly different from normal; however, in the remaining children with chemical diabetes, those with elevated TIRI, the IRP was elevated following glucose administration. Although the IRP was significantly elevated in the hyperinsulinemic group, the TIRI was also increased to such an extent that the glucose intolerance demonstrated in these patients could not be attributed to the elevated IRP.

Adolescent↗
PubMed1976

Inhibition of insulin degradation by nonsuppressible insulin-like activity.

Nonsuppressible insulin-like activity, provided by three sources, was evaluated for its effect on the proteolytic degradation of insulin utilizing insulin protease obtained from rat liver homogenate as well as liver cell membranes. All three preparations of nonsuppressible insulin-like activity were found to be competitive inhibitors of insulin degradation. In addition human plasma was fractionated yielding an acetone precipitate which was found to have nonsuppressible insulin-like activity and to be a competitive inhibitor of insulin protease.

Animals↗
PubMed1976

Comparison of the effectiveness of various routes of insulin injection: insulin levels and glucose response in normal subjects.

The difference in absorption of insulin and its glucose lowering-effect after the administration of crystalline insulin by the intravenous, intramuscular, and subcutaneous routes was compared in 14 lean normal subjects. Insulin in a dose of 0.1 U/kg body weight was given by the three different routes. Blood was drawn from the opposite arm at regular intervals for the determination of insulin, glucose, glucagon, cortisol, and potassium. Intravenous insulin produced the highest pharmacological level of insulin in 2 minutes (2099 +/- 414 muU/ml) with marked hypoglycemia at 30 minutes (a 68% drop). Intravenous insulin injection produced an increase in plasma glucagon and cortisol reaching a 2-fold increase above the fasting level 30 minutes after the glucose nadir. An equivalent amount of intramuscular insulin produced a maximal increase in plasma insulin at 50 minutes (45 +/- 4 muU/ml) and caused a 35% drop in plasma glucose at 60 minutes, which effects were greater than those caused by subcutaneous injection (highest IRI = 36 +/- 3.5 muU/ml and 23% glucose drop at 180 minutes). No significant increase in glucagon or cortisol was noted with equivalent amounts of subcutaneous or intramuscular insulin injection. Our studies suggest that, in normal lean subjects, insulin injection by the intramuscular route provides a faster absorption of insulin with a concomitant greater drop in plasma glucose than does injection by the subcutaneous route.

Absorption↗
PubMed1976

The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis.

The effect of low-dose intramuscular insulin therapy was compared with that of high-dose insulin therapy by intravenous and subcutaneous routes in 48 patients with diabetic ketoacidosis. A simplified protocol was devised to compare efficacy of the two methods of therapy in a randomized manner. Plasma glucose dropped to less than 250 mg/dl in the low-dose group in 6.7 +/- 0.8 h and in the high-dose group in 4.5 +/- 0.8 h (P = not significant). The amount of insulin necessary to lower plasma glucose to 250 mg/dl was 263 +/- 45 U in the high-dose group and 46 +/- 5 U in the low-dose group. Twenty five percent in the high-dose group and none in the low-dose group developed hypoglycemia. Other biochemical and clinical variables in the two groups were comparable. No treatment complications were noted in the low-dose group. Our studies suggest that low-dose intramuscular insulin therapy is simple and as effective as high-dose therapy in the treatment of diabetic ketoacidosis without the risk of hypoglycemia and with a diminished incidence of hypokalemia. Furthermore, the favorable response of these patients to low-dose insulin therapy suggests the absence of insulin resistance in diabetic ketoacidosis.

Adolescent↗
PubMed1976

The effect of age on plasma proinsulin-like material after oral glucose.

The total plasma insulin and proinsulin-like material after oral glucose was studied in 68 lean subjects of varying ages with normal glucose tolerance tests. Although each subject had a normal test, the mean glucose levels increased with increasing age. When younger subjects (ages 15 to 44) were compared with older (45 to 74), no significant differences in total insulin responses were seen, but plasma proinsulin-like material was significantly higher in the older age subjects. All values after stimulation were significantly greater in subjects 45 to 74 years of age than in those 15 to 44 years of age (p less than 0.01). A significant correlation between the amount of proinsulin and the age of the subject was seen. These findings may reflect a decreased conversion of proinsulin to insulin in the aging pancreas or could reflect decreased clearance of proinsulin in older subjects.

Administration, Oral↗
PubMed1975

Effect of steroidogenesis on ascorbic acid content and uptake in isolated adrenal cells.

Isolated adrenal cell preparation was used to investigate the relationship between ascorbic acid and steroidogenesis by two methods: (1) in vivo incorporation of exogenous [1-14C]ascorbic acid into endogenous ascorbic acid of adrenal by intraperitoneal injection of labeled ascorbic acid into rats and studying the depletion of labeled ascorbic acid under a variety of experimental conditions; and (2) study of the uptake of [14C]ascorbic acid by IAC in response to steroidogenic stimuli and various steroids. These studies demonstrate that: 1. IAC preparation by the trypsin digestion method results in almost total depletion of ascorbic acid from adrenal cells, i.e., ascorbic acid content of the cell preparation was less than 1% of the original ascorbic acid in quartered adrenal gland. 2. In spite of such a severe depletion of ascorbic acid, steroidogenesis in response to ACTH and dibutyryl cyclic AMP (dcAMP) is quite pronounced. 3. ACTH and dcAMP affect depletion of endogenously labeled ascorbic acid in IAC by a process that is both concentration- and time-dependent, but is independent of steroidogenic processes. 4. ACTH and dcAMP both inhibit the uptake of exogenous [1-14C]ascorbic acid, which is time-dependent but independent of the steroidogenic phenomenon. 5. The uptake of [14C]ascorbic acid by IAC is independent of extra-to-intracellular gradient of glucocorticoids or mineralocorticoids.

Adrenal Glands↗
PubMed1975

Effect of ascorbic acid on ACTH-induced cyclic AMP formation and steroidogenesis in isolated adrenal cells of vitamin E-deficient rats.

Isolated adrenal cells from Vitamin E-deficient and control rats were prepared by a trypsin digestion method. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) formation was studied in response to adrenocorticotropin (ACTH) in the presence and absence of ascorbate by measuring the conversion of prelabeled adenosine 5'-triphosphate [14C]ATP to cyclic [14C]AMP. Ascorbate (0.5 mM) inhibited ACTH-induced cyclic [14C]AMP formation in adrenal cells isolated from Vitamin E-deficient rats but had no effect in the control cells. The inhibitory effect of ascorbate on ACTH-induced cyclic AMP formation in Vitamin E-deficient rats decreased as the concentration of ACTH increased. In Vitamin E-deficient rats ascorbate inhibited ACTH-induced cyclic [14C]AMP formation after 30 min of incubation. There was no further significant accumulation of cyclic [14C]AMP at 60 min or 120 min although in the absence of ascorbate cyclic [14C]AMP continued to be formed. The in vitro addition of alpha-tocopherol reduced the inhibition of ACTH-induced cyclic [14C]AMP formation by ascorbate in Vitamin E-deficient rats. These studies suggest that alpha-tocopherol and ascorbate may affect ACTH-induced cyclic AMP formation through interaction with the membrane-bound enzyme adenylate cyclase.

Adrenal Glands↗
PubMed1975

Proteolytic degradation of insulin and glucagon.

The degradation of insulin and glucagon by a highly purified enzyme isolated from rat skeletal muscle was investigated. A sensitive assay for proteolytic degradation of insulin and glucagon using fluorescamine to detect an increase in primary amine groups was established. As measured by an increase in fluorescamine reactive materials, insulin was rapidly degraded by this highly purified enzyme without requiring initial disulfide cleavage. Associated with the increase in fluorescamine reactive materials was a decrease in immunoassayable insulinmglucagon wal also proteolytically degraded by this enzyme but a number of other peptides and proteins including proinsulin, and A and B chains of insulin were not degraded. Thus, we have demonstrated that insulin (and glucagon) can be proteolytically degraded by an enzyme isolated from an insulin sensitive tissue, skeletal muscle. Proteolytic degradation by this enzyme requires the intact insulin molecule rather than separate A and B chains.

Animals↗
PubMed1975

Allergic response to glucagon injection as a result of insulin contamination.

A 25-year-old obese woman with adult onset diabetes, with known insulin allergy, was evaluated for her insulin response to glucagon. Intravenous injection of glucagon produced severe generlaized allergic reaction. Skin tests with various insulin and glucagon preparations showed allergic reaction to be most pronounced with beef regular single peak and single component insulin, pork regular single peak, beef lente single peak, and neutral regular (beef-pork) single peak insulin. Allergic reactions to numerous glucagon preparations were found to be directly proportional to the amount of insulin contamination in those preparations. Purification of one glucagon lot by column chromatography verified the presence of proinsulin and insulin contaminants in the preparation.

Adult↗