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Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Exogenous insulin therapy slows weight loss in type 2 diabetic patients.

The impact of exogenous insulin therapy on the ability of obese, noninsulin dependent diabetic patients to lose weight was studied. Weight loss data from seven insulin-requiring type 2 diabetic patients, 11 sulfonylurea-treated type 2 diabetic patients and 12 non-diabetic controls on very-low-calorie diets were analyzed. Upon starting the diet, insulin doses were reduced by 50 percent and given once daily as intermediate-acting insulin. Doses were adjusted to maintain capillary blood glucoses between 6.7 and 10 mM. Sulfonylureas were stopped upon initiation of the diet. Patients were seen weekly for determination of their dietary compliance, medical status, glucose control, activity level and amount of weight loss. The insulin-treated subjects lost significantly less weight per week, whether expressed as kilograms, change in body mass index or percent of initial body weight lost. Treatment of obese type 2 diabetic patients with insulin retards their ability to lose weight independent of caloric intake.

Adult↗
PubMed1987

In vivo insulin antagonism but evanescent in vitro tissue effect in rats with growth hormone-secreting tumors.

Rats bearing mammosomatotropic tumors have raised insulin but lowered glucose concentrations. To determine if growth hormone (GH) secreted by these tumors causes insulin antagonism, pancreatic suppression tests utilizing infusions (per kg per min) of glucose (8 mg), insulin (200 ng) and somatostatin (1.4 micrograms) for 130 min were performed. Although the steady state plasma glucose and insulin levels (mean of 90, 100, 110, 120 and 130 min samples) were similar in 8 control and 13 tumor-bearing rats, the decrease from the already depressed basal glucose concentration (mmoles/l +/- SE) in the tumor animals was less than in the controls (0.90 +/- 0.30 vs. 2.56 +/- 0.040, p less than 0.005). Since the interpretation of these results was not entirely clear, glucose and insulin-glucose tolerance tests were performed. The glucose disappearance rates (%/min +/- SE) in the glucose tolerance test were lower in 17 tumor rats (2.00 +/- 0.13) compared to 17 control animals (2.51 +/- 0.22). This difference just missed statistical significance (t = 2.00, value of 2.04 necessary for p = 0.05). The decrease occurred in the presence of increased insulin (nmoles/l X 16 min) levels (4.29 +/- 0.38 vs. 2.58 +/- 0.29, p less than 0.005) suggesting insulin antagonism. The glucose disappearance rates (%/min +/- SE) in the insulin-glucose tolerance test were less in 12 tumor-bearing rats compared to 11 control animals (2.80 +/- 0.29 vs. 4.12 +/- 0.35, p less than 0.02). Thus, these GH-secreting tumors cause insulin antagonism in vivo. Freshly isolated hepatocytes from these tumor-bearing animals manifest decreased insulin binding and action (Diabetologia 25:60, 1983). In the present study, however, insulin binding and action (net glucose-C14 incorporation into glycogen) were normal after the hepatocytes were cultured for two days. This suggests that the changes induced by GH in vivo that lead to insulin antagonism are short-lived.

Animals↗
PubMed1987

Idiopathic fasting hypoglycemia in an adult.

A 73-year-old man with documented and persistent fasting hypoglycemia for at least 22 years underwent extensive study including percutaneous liver biopsy for measurement of selected enzymes. No known cause of fasting hypoglycemia could be found. This is believed to be the first reported case of "idiopathic" fasting hypoglycemia in an adult. At the present time, it is not possible to classify the cause of this patient's hypoglycemia due to incomplete understanding of the abnormalities of carbohydrate metabolism.

Aged↗
PubMed1987

Possible role for the glucose-fatty acid cycle in dexamethasone-induced insulin antagonism in rats.

This study was undertaken to elucidate the mechanism(s) involved in glucocorticoid-induced insulin antagonism. Male Sprague-Dawley rats (200 to 210 g) were injected with 1 mg/kg dexamethasone-phosphate (Dex) or the vehicle every other day for 10 days. Two days after the last injection, fasted anesthetized animals were infused (per kg body weight per min) with 8 mg glucose, 5 mU porcine insulin and 1.4 micrograms somatostatin with blood sampling before, and at 10 min intervals between 90 and 130 min after the pancreatic suppression test was begun. At the end of the test, abdominal muscle was quickly freeze-clamped and the substrate and products of the rate-determining reactions of glycolysis and glycogenesis were measured. Dex-treated rats had higher basal (0 min) and steady-state levels (90-130 min) of both glucose and insulin signifying insulin antagonism. The pattern of muscle tissue metabolites revealed no free intracellular glucose in either group and concentrations of all other metabolites in the Dex-treated rats were less than those in the control animals (except for a small increase in glycogen). These results suggest a site of insulin antagonism between (and including) insulin binding and glucose transport. Further studies in the Dex-treated rats revealed normal: a) insulin binding to freshly isolated hepatocytes; b) basal and insulin-stimulated xylose transport in soleus muscle; c) basal and insulin-stimulated glucose uptake in hemidiaphragms. These normal in-vitro results suggested that a circulating factor may be responsible. Repeat pancreatic suppression tests in the Dex-treated rats revealed blunted suppression of serum FFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Effect of glyburide on glycogen metabolism in cultured rat hepatocytes.

Sulfonylurea agents decrease hepatic glucose production and fasting glucose levels in type II diabetic patients without changing fasting insulin concentrations. This raises the possibility that these drugs may act directly on hepatic carbohydrate metabolism. Cultured rat hepatocytes were used to test this hypothesis. To ascertain whether this in vitro system was suitable to demonstrate an effect of sulfonylurea agents (eg, the well-documented insulin-potentiating action), we initially measured the effect of glyburide (2 micrograms/mL) on insulin-stimulated net glucose-14C incorporation into glycogen. Glyburide increased sensitivity to insulin (ie, shifted the dose-response curve to the left) without affecting either responsiveness or insulin binding. Thus, the ED50 was significantly lowered (8.4 v 15.2 ng/mL), whereas the percent increase (181% v 170%) over the basal level, specific tracer insulin binding (5.3% v 5.1% per mg protein), and the Scatchard plots were similar. Since an effect of sulfonylurea agents could be demonstrated in this system, and the glycogen pathways supply 75% of hepatic glucose production after an overnight fast, we next measured the direct effect of glyburide (2 micrograms/mL) on glycogen storage and breakdown. Glycogenolysis was assessed by measuring the breakdown of prelabeled glycogen (from galactose-14C) and glycogen synthesis by the incorporation of glucose-C14 into glycogen. Glyburide significantly inhibited glycogenolysis and stimulated glycogen synthesis. Furthermore, glyburide significantly stimulated glycogen synthase while glycogen phosphorylase was unaffected. In conclusion, glyburide directly inhibited glycogenolysis, stimulated glycogen synthesis and glycogen synthase, and potentiated the action of insulin on glycogen synthesis at a postbinding site in cultured rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inverse relationship of metabolic clearance rate of insulin to body mass index.

Twenty-five human subjects, whose body mass indices (BMI) ranged from 18.0 to 34.1 kg/m2, underwent euglycemic clamps at both low (1.5 mU/kg/min) and high (10 mU/kg/min) insulin infusion rates. Mean C-peptide concentrations were less than or equal to 0.5 ng/mL at the end of each two-hour period. The metabolic clearance rates (MCR) of insulin (mL/kg/min) were significantly (P less than .001) inversely correlated with BMI at both the low (r = -.65) and high (r = -.71) insulin infusion rates. The negative inverse correlations with BMI remained significant at both the low (r = -.42, P less than .05) and high (r = -.61, P less than .005) insulin infusion rates if the MCR were expressed as mL/m2/min. There were no significantly correlations (r less than .21) between the MCR at either rates of insulin infusion and age or tracer insulin binding to monocytes. Decreased MCR of insulin may contribute to the hyperinsulinemia seen in obese subjects.

Adult↗
PubMed1987

Kaluresis independent K homeostasis in dogs: activity after ureter ligation and pancreatectomy.

In ureter ligated dogs intravenous administration of KCl stimulates both insulin secretion and activity of a kaluresis independent K homeostatic mechanism (K transfer capacity) that retards the development of hyperkalemia by transferring K to intracellular fluid. If the preparation is K loaded by infusion with 2 mEq KCl/kg/hr until prelethal ECG changes of hyperkalemic cardiotoxicity appear, about 50% of administered K is transferred. An increased proportion--70%--is transferred if the animal is K loaded 70 minutes after pancreatectomy--when serum immunoreactive insulin is fixed at less than 4 uU/ml. That proportion (70%) is unchanged by simultaneous adrenalectomy, but is reduced to less than 40% by propranolol blockade of B receptors. Increased post pancreatectomy K transfer capacity apparently involves K transfer mediated by B receptors that are activated by an extra-adrenomedullary B agonist(s). Findings also indicate that residual post pancreatectomy insulin biological activity mediates K transfer.

Animals↗
PubMed1987

The role of glucosylated serum albumin in monitoring glycemic control in stable insulin-requiring diabetic out-patients.

To determine the value of glucosylated serum albumin (GSA) in assessing blood glucose control in stabilized diabetic out-patients, 15 insulin-requiring subjects were studied for 8-12 weeks. GSA was determined every 14 days, and glucosylated hemoglobin (GHb) was measured once or twice. Capillary blood glucose records were used to determine mean fasted and mean daily blood sugar concentrations (mean of fasted, preprandial, and bedtime values) during serial 7-day intervals preceding each GSA and GHb determination and also for 28-, 56-, and 84-day intervals preceding each GSA determination. GSA positively correlated with preceding weekly mean fasting and mean daily blood glucose concentrations for 1-11 weeks (r ranges, 0.40-0.64 and 0.46-0.64, respectively) without a temporal pattern. GSA positively correlated with mean fasted and daily blood sugar levels determined over the preceding 28, 56, and 84 days (r range, 0.54-0.74). In addition, GSA correlated with GHb when drawn within 14 days (r = 0.72) or 28 days (r = 0.65) of each other. When monitoring the glycemic control of stable insulin-requiring diabetic patients, GSA offers similar information to GHb, and the two tests may be used interchangeably.

Adult↗
PubMed1986

Augmented aldosterone and insulin responses to potassium infusion in dogs with renal failure.

The present study examines acute potassium-induced insulin and aldosterone responses in renal failure, and the role of chronic dietary potassium intake in modifying these acute responses. Plasma aldosterone (PA) and insulin (IRI) responses to acute KCl infusion were examined in control and remnant kidney dogs on two potassium intakes. Dogs (N = 8) received the KCl infusions after 10 days of a 60, and then 10 days of a 200, mEq daily potassium intake during control and after surgical-induced renal failure (CRF). A one hour intravenous infusion of KCl (2 mEq KCl/kg/hr) in dextrose and water was performed with blood samples for PA, IRI, creatinine and electrolytes, and urine for electrolytes and creatinine at 20 minute intervals one hour preceding, during, and after the infusion. Preinfusion PA was higher (P less than 0.05) in controls and CRF dogs on 200 mEq potassium intake compared to 60 mEq potassium intake. The peak incremental responses of PA to KCl infusion were increased (P less than 0.01) in CRF compared to controls on 60 mEq (PA 36 +/- 4.2 vs. 26 +/- 3.0 ng/dl) and 200 mEq (delta PA 49 +/- 5.6 vs. 37 +/- 2.8 ng/dl) potassium intakes. Differences in incremental PA responses in CRF were not due to altered aldosterone metabolic clearance rates, changes in renin, or ACTH activity. Pre-infusion IRI was higher (P less than 0.05) in CRF than control dogs on both potassium diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Kaluresis independent K-homeostasis: glucagon and B receptor blockade in pancreatectomized dogs.

Seventy minutes post pancreatectomy, in dogs that are K loaded - made abruptly hyperkalemic and "life threatened" - by infusion with 2 mEgKC1/kg-/hr until prelethal ECG changes of hyperkalemic cardiotoxicity appear, a kaluresis independent K homeostatic mechanism transfers about 2/3 of administered K to intracellular fluid. Treatment of K loaded pancreatectomized dogs with glucagon or a B receptor blockading dosage of propranolol does not alter the proportion transferred, but treatment with glucagon and propranolol reduces it. It appears that in pancx dogs there is a reciprocal relation between insulin and B receptor mediated K transfer and that glucagon is involved in activity of the kaluresis independent K homeostatic mechanism.

Animals↗
PubMed1986

Pathogenesis of type 2 diabetes mellitus: an interpretation of current data.

The available evidence concerning the pathogenesis of type 2 diabetes mellitus suggests that although insulin antagonism is common to many patient groups (i.e., obese, older), overt NIDDM will only develop in a subset who may have a genetic susceptibility for inadequate beta-cell reserves. Since the role of a receptor defect in causing type 2 diabetes is doubtful, the insulin antagonism in these patients is due to a post-receptor defect.

Adult↗
PubMed1986

Protein phosphorylation in a myogenic cell line: effects of insulin, epinephrine and glucose.

Protein phosphorylation was studied in L6 cultured muscle cells by incubating cells with Na 32Pi and subsequently exposing them to external agents. L6 cells readily incorporated 32Pi into a number of peptides approaching steady-state incorporation by 2 h. Insulin stimulated the phosphorylation of one peptide of molecular mass 29,000 daltons by 37% with an ED50 of 3 mU/ml. This peptide was located in the high-speed pellet (105,000 g 60 min) which is consistent with an S6 ribosomal protein. Epinephrine (10(-5) M) led to only a modestly stimulated (less than 14%) phosphorylation of three peptides of molecular masses 39,000, 29,000 and 21,000 daltons. Glucose (5-50 mM) stimulated the phosphorylation of one peptide of molecular mass 19,000 daltons by 24%.

Autoradiography↗
PubMed1986

Insulin antagonism is not a primary abnormality of amyotrophic lateral sclerois but is related to disease severity.

Sensitivity to insulin was studied in 13 patients with amyotrophic lateral sclerosis (ALS) and 10 age- and weight-matched normal subjects by performing euglycemic clamp studies at low (1.5 mU/kg X min) and high (10 mU/kg X min) insulin infusion rates. Mean glucose disposal rates were similar in the ALS patients and normal subjects at both the low [4.8 +/- 0.6 (+/- SEM) vs. 5.2 +/- 0.6 mg/kg X min] and high (9.2 +/- 1.3 vs. 9.8 +/- 0.5 mg/kg X min) insulin infusion rates, respectively. Binding of [125I] iodoinsulin to monocytes was also similar in seven patients with ALS (3.8 +/- 1.0%/10(7) cells) and 10 normal subjects (3.9 +/- 0.9). However, glucose disposal rates correlated inversely with disease severity in the ALS patients, at both the low (r = -0.76; P less than 0.01) and high (r = -0.83; P less than 0.001) insulin infusion rates. We conclude that insulin antagonism is not a primary abnormality of ALS, but may be related to the inactivity associated with disease progression.

Adult↗
PubMed1985

Insulin secretion and action in the hyperthyroid rat.

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.

Animals↗
PubMed1985

Hyperthyroid Graves' disease causes insulin antagonism.

Oral glucose tolerance and pancreatic suppression tests were carried out in six young hyperthyroid men before treatment and 2-4 weeks after thyroid function tests returned to normal and in six normal men matched for age and weight. Glucose intolerance was present in the hyperthyroid individuals. It improved, but did not return to normal, after treatment. Insulin secretion was increased, and the peak values were delayed in the patients. Treatment did not influence the amount or pattern of the insulin response. Steady state plasma glucose levels (milligrams per dl +/- SEM) were significantly (P less than 0.001) higher in the hyperthyroid patients before treatment (128.6 +/- 2.4) than in the normal subjects (86.1 +/- 3.1). Although after treatment, steady state plasma glucose levels (116.1 +/- 2.7) decreased significantly (P less than 0.001), they remained higher than those in normal subjects (P less than 0.01). Therefore, insulin action was impaired in hyperthyroidism and had not returned to normal by 2-4 weeks after thyroid function tests were in the normal range.

Adult↗