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At least 19 recordsLinked to original sources
PubMed1978

Insulin tolerance in rats.

Insulin tolerance was studied in young (8- to 10-week-old) Wistar rats: a) after the administration of mounting doses of long-acting insulin (10, 40, 160 and 320 units/kg bw.) to animals fed ad libitum on two different diets); b) after the administration of long-acting insulin (1 and 5 units/kg b.w.) to animals which had fasted for different lengths of time. In rats fed ad libitum on the two diets, graded doses of insulin induced (except for the smallest dose) hypoglycaemia of roughly the same intensity, but varying in duration in correlation to the dose. The administration of insulin to fasting rats showed differences in insulin tolerance which were correlated to the duration of the fast. A significant decrease in insulin tolerance was already found after 6 hours. During the given testing period (72 hours), the lowest insulin tolerance was found after a 12 hours' fast and the highest after 48 hours. Insulin tolerance after 24 and 72 hours' fasting was approximately the same; it was higher than after 12 hours, but lower than after 48 hours. The initial blood sugar level (before administering insulin) was not in any way correlated to insulin tolerance determined at various intervals during fasting.

Animals↗
PubMed1977

Hypoglycaemia and food intake in rats given graduated doses of insulin.

Hypoglycaemia of varying duration was induced with graduated doses of long-acting insulin (10, 40 and 160 U/kg b.w.) in young, growing (8- to 10-week-old) male Wistar rats fed ad libitum on two different diets. In all, 6 doses of insulin were administered, at 48-hour intervals. The blood glucose level and food consumption were determined 3, 6, 12, 24 and 48 hours after injecting the insulin. Both the hypoglycaemic effect and elevated food intake during hypoglycaemia depended on the dose of insulin and not on the type of diet. Total food consumption during the experiment (12 days) was markedly raised only in the groups given the maximum dose of insulin (160 U/kg b.w.). The weight gain in all the experimental groups was lower than in the control groups and food consumption per weight gain unit was higher.

Animals↗
PubMed2026

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100&#x2009;U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24&#x2009;weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (<&#x2009;65, &#x2265;&#x2009;65&#x2009;years), T2D duration (<&#x2009;10, &#x2265;&#x2009;10&#x2009;years) and HbA1c (&#x2265;&#x2009;7% to &#x2264;&#x2009;8% [&#x2265;&#x2009;53 to &#x2264;&#x2009;64&#x2009;mmol/mol], >&#x2009;8% to &#x2264;&#x2009;9% [>&#x2009;64 to &#x2264;&#x2009;75&#x2009;mmol/mol], >&#x2009;9% [>&#x2009;75&#x2009;mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n&#x2009;=&#x2009;291; IDegAsp n&#x2009;=&#x2009;291), baseline age was <&#x2009;65&#x2009;years in 442 and &#x2265;&#x2009;65&#x2009;years in 140; T2D duration was <&#x2009;10&#x2009;years in 366 and &#x2265;&#x2009;10&#x2009;years in 216; and HbA1c was &#x2265;&#x2009;7% to &#x2264;&#x2009;8% in 205, >&#x2009;8% to &#x2264;&#x2009;9% in 209 and >&#x2009;9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans↗
PubMed1977

Pulmonary insulin responsivitiy: in vivo effects of insulin on the diabetic rat lung and specific insulin binding to lung receptors in normal rats.

Adult rats were rendered diabetic by a single iv injection of streptozotocin (70 or 75 mg/kg). In these rats, serum insulin fell to minimal levels during the 48 h following drug treatment, and this was roughly paralleled by a progressive decrease in the ability of the lung to oxidize glucose. The addition of insulin to diabetic rat lung slices in vitro had no restorative effect on the depressed glucose oxidative rate during a 2 h incubation period; however, two daily treatments of the rats with 1 unit of protamine, zinc insulin completely restored lung glucose oxidation rate to normal, without significantly reducing the hyperglycemic state of the rats. An examination of the temporal changes in glucose utilization by the rat lung after acute insulin treatment revealed that the diabetic lung responded directly to serum levels of insulin, whereas the normal lung appeared to be unaffected by serum insulin levels as hihg as 87 ng/ml. The reduced rate of glucose oxidation in the diabetic lung was apparent after perfusion of the lung with glucose-free medium, and was characterized by a significant reduction in Vmax without an alteration in Km. This was attended by a depressed ability of the lung to incorporate [3H]leucine into protein and an increased ability to produce lactate, but hexose monophosphate shunt activity was normal. Specific receptors for insulin have been identified and partially characterized in crude membrane preparations of normal rat lung. The interaction of insulin with these receptors was rapid, reversible, saturable, and was dependent upon time and temperature. The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts. These observations suggest that insulin regulates the transport and utilization of glucose in the rat lung, and that this tissue contains specific receptors for insulin.

Animals↗
PubMed1976

Total pancreatectomy for ductal carcinoma of the head of the pancreas: current status.

Because of dismal results after pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas, a review was made of patients treated by total pancreatectomy for this condition. Although the early experience with total pancreatic resection was disappointing, the results during the past decade have been encouraging. Among the forty-two patients reported on with sufficient detail for analysis the operative mortality has been 17 per cent, and the morbidity has been 21 per cent. Sixty-five per cent of these patients (20 of 30) have survived at least one year and 53 per cent (16 of 30) have lived at least two years after surgery. The management of the diabetes and pancreatic insufficiency has not been difficult. Total pancreatectomy appears to be preferable to pancreaticoduodenectomy in the treatment of ductal carcinoma of the head of the pancreas.

Aged↗
PubMed1977

Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities.

The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.

Animals↗
PubMed1978

Insulin treatment in diabetes.

Efficacy of and indications for the use of purer forms of insulin have now been established, and arguments showing the relation of blood glucose control to the development and progression of complications have been strengthened.

Adipose Tissue↗
PubMed1977

Diabetes: The quest for basal normoglycaemia.

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycaemia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycaemia has been obtained with markedly reduced plasma-glucose levels during the day. Plama-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycaemia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycaemia.

Adult↗
PubMed1975

Aspects of the adrenal function in the domestic fowl.

Chromatographic purification of extracts of hen peripheral plasma on Florisil columns before measurement by spectrofluorometry showed a basal level for corticosterone of 1-3 mug/100 ml, which is much lower than concentrations previously reported using acid fluorescence. Neither handling, restraint nor repeated bleeding affected the concentration of this hormone or of glucose. Adrenal function tests with two preparations of synthetic corticotrophin showed that they caused a rapid rise in blood corticosterone and eventually of glucose. Results of studies using insulin or tolbutamide i.v. suggest that there is a threshold concentration of plasma glucose (about 70 mg/100 ml) below which hypoglycaemia stimulates the hypothalamic-pituitary-adrenal system in fowls. Prolonged treatment of laying hens with protamine zinc insulin led to aphagia and cessation of egg-laying; increased concentrations of corticosterone were observed 2 days after the administration of insulin ceased, coinciding with the return to normal plasma levels of glucose. 'Chemical adrenalectomy' with metyrapone showed that the restoration of plasma glucose to a normal concentration after insulin treatment is dependent upon fully functional adrenal cortical tissue. It appears likely that the adrenal medulla is a target for corticosterone which probably regulates the tissue levels of phenylethanolamine-N-methyltransferase, one of the enzymes necessary for the biosynthesis of adrenaline.

Adrenal Cortex Function Tests↗
PubMed1976

Insulin allergy: an approach to therapy.

Insulin can evoke local and systemic hypersensitivity responses after injection. Many individuals receiving commercial insulin preparations experience local reactions, usually of short duration. A case of severe, persistent insulin-induced skin allergy and the use of therapy, including hyposensitization, to alleviate symptoms are discussed.

Animals↗
PubMed1978

The effect of induced hyperglucagonaemia on the Zucker fatty rat.

The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.

Adenosine Triphosphatases↗
PubMed1977

Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of langerhans.

1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [(3)H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2-20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5-20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [(3)H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2-20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on beta-cell function.

Animals↗
PubMed1979

Elevated serum proinsulin in beta cell nesidioblastosis. Report of a case in a newborn.

A newborn infant with severe hypoglycaemia and nesidioblastosis was subjected to subtotal pancreatectomy without any sign of improvement. In spite of very low plasma levels of glucose (i.e. less than 1 mmol/l) plasma insulin concentrations were high (i.e. greater than 700 pmol/l). Plasma proinsulin was considerably enhanced comprising 43% of the total insulin immunoreactivity. Plasma glucagon concentrations were normal. Postoperatively normal to subnormal plasma glucose levels could only be maintained by treatment with frequent meals, diazoxide and intramuscular injections of a long-acting glucagon preparation. With time, signs of mental retardation became obvious.

Adenoma, Islet Cell↗
PubMed1979

[Studies on the radioreceptor assay of TSH: the binding of 125I-TSH to the human thyroid receptor and the interaction of LATS-IgG (author's transl)].

The radioreceptor assay system for TSH is considered to be useful in quantitating the hormone and analyzing the mechanism of its action. The assay was established, and the interaction of abnormal thyroid stimulators in Graves' patients was evaluated in this assay system. A 10,000xg fraction of human thyroid homogenates was used as the receptor. Human TSH supplied from NIH was iodinated by using lactoperoxidase. The binding of 125I-TSH to the receptor was small, and 125I-TSH was further purified by the receptor binding. The receptor (25mg equivalent), purified 125I-TSH, and standard TSH or a sample were incubated at 37 degrees C for 60 min in a final volume of 300 microliters. The binding of 125I-TSH to the receptor was time- and temperature-dependent with optimal binding under the conditions described above. The binding was completely inhibited by the addition of human, bovine and ovine TSH and partially inhibited by high concentrations of HCG, FSH-LH. However, there was no cross reactivity with insulin, prostaglandin E1, E2, T3, T4 and Nal. The assay was sensitive enough to detect 5 to 50 microU of TSH. The amount of TSH bound to the receptor was almost parallel to the TSH concentration which is necessary to stimulate human thyroid adenylate cyclase activity. Studies of dissociation kinetics and Scatchard plot indicated that there were two classes of TSH receptors in the human thyroid. A higher association constant was calculated as 1.5 x 10(8)M-1. LATS-IgG from a patient with Graves' disease completely inhibited the binding of 125I-TSH to the receptor, and studies of Lineweaver-Burk, plot suggested that TSH and LATS-IgG shared common binding sites. The radioreceptor assay of TSH appears to be useful in evaluating the abnormal thyroid stimulators present in Graves' disease.

Binding, Competitive↗