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Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

198 records · Page 11Linked to original sources
PubMedDate not supplied

Hepatic effects of glucose and insulin independent of cyclic nucleotide changes.

To determine if cGMP might function as a second messenger for insulin, an in situ liver perfusion system was established in which hepatic effects of insulin could be correlated with changes in cyclic nucleotides. Several combinations of insulin (10 mU/ml) and glucose (50 mg/ml) were infused (0.1 ml/min) for 30 min into fasted normal and diabetic rats with removal of a similar volume of blood. Samples of livers were removed at the beginning and end and at various times during the perfusion. In normal animals perfused with buffer alone, hepatic glycogen content fell. When glucose (with or without added insulin) was added to the perfusate, glycogen levels rose. With buffer alone, there was no change in the independent (I) form of glycogen synthase at 10 min but a modest increase at 30 min. With insulin and/or glucose, there as a large increase in the I-form of the enzyme at 10 min and a further rise at 30 min. Neither cGMP nor cAMP changed even though tissue samples were obtained at multiple times throughout the perfusion. Cyclic nucleotides were also measured in liver slices exposed to insulin (1 mU/ml) after 30 min of pre-incubation for stabilization. Although significant increases in cGMP were noted in the tissue exposed to insulin, similar significant rises also occurred in appropriately paired control slices. When glucagon was used in both the in situ perfusion and the paired liver slice systems, the expected rapid and large increases in cAMP levels occurred attesting to the validity of both approaches in evaluating hepatic cyclic nucleotide responses. These results plus the paucity of convincing data in the literature strongly suggest that cGMP can no longer be considered a candidate for the putative second messenger of insulin.

Animals↗
PubMedDate not supplied

Lipid metabolism by muscle of diabetic rats.

This study was undertaken to ascertain whether enhanced oxidation of intracellular lipids could explain the impaired carbohydrate metabolism of diabetes. Pieces of diaphragms removed from diabetic (60--75 mg/kg streptozotocin i.v.) and control rats were incubated for 1 h with palmitate-1-14C. Tissue lipids from one piece were separated on silicic acid columns and the amount and specific activity of free fatty acids (FFA), triglycerides (TG) and phospholipids (PL) were measured. 14CO2 production was also assessed in some experiments. The other pieces of tissue were incubated for a subsequent hour (without radioactivity) at which time measurements of tissue lipid content and specific activity and 14CO2 production were again performed. FFA incorporation into CO2, tissue TG and PL was normal. TG content was moderately and PL content was slightly reduced in diabetic tissue. Changes in diaphragm TG and PL content and specific activity during the 2nd h of incubation strongly suggested that most of the 14CO2 produced during this period was derived from TG. Approximately 25% of tissue TG in both control and diabetic muscle was oxidized to CO2 during the 2nd h of incubation. In diaphragms from diabetic rats, (+)-octanoylcarnitine (an inhibitor of FFA oxidation) decreased TG oxidation considerably but had no effect on the impaired glucose uptake. Thus, these data do not support the hypothesis that the glucose-fatty acid cycle (utilizing either extra- or intracellular lipids) may account for the altered carbohydrate metabolism of diabetic muscle.

Animals↗
PubMedDate not supplied

Small doses of intracarotid insulin do not lower plasma glucose in the rat.

We sought to confirm the observation that 500 microU of insulin injected into the carotid artery of rats lowers plasma glucose by approximately 20 mg/dl within 2 minutes. In our hands, glucose concentrations fell gradually by approximately 20-25 mg/dl over a 45-60 minute period after insertion of a carotid artery cannula. This occurred whether 500 microU of insulin and/or anti-insulin serum or saline were injected toward the heart. There was no change in glucose concentrations following injection of 500 microU of insulin toward the head 45 minutes after insertion of the cannula. Thus, the hypoglycemic response to small amounts of insulin administered to the head via the carotid artery must be very sensitive to factors that are currently difficult to recognize.

Animals↗
PubMedDate not supplied

Moderate insulinopenia can cause insulin antagonism.

Profound insulin deficiency can cause insulin antagonism. To assess whether more modest insulinopenia can also cause insulin antagonism, male Sprague-Dawley and female obese (fa/fa) Zucker rats received streptozotocin injections (20, 30 or 40 mg/kg) or citrate buffer alone. After 1 and 2 weeks, the animals underwent glucose (0.5 g/kg) and insulin (0.2 U/kg)-glucose (0.7 mg/kg) tolerance tests, respectively, after an overnight fast. In the Sprague-Dawley rats: (a) basal glucose concentrations were significantly increased in the 40 mg/kg group; (b) glucose-induced insulin responses were significantly decreased in the 30 and 40 mg/kg groups; (c) glucose disappearance rates after glucose alone were significantly decreased in the 40 mg/kg group; and (d) glucose disappearance rates after insulin and glucose were significantly decreased in both the 30 and 40 mg/kg group. All obese Zucker rats injected with 30 and 40 mg/kg died within the first week with marked hyperglycemia. In the 20 mg/kg groups: (a) basal glucose levels were significantly elevated; (b) glucose disappearance rates and insulin responses were significantly decreased; (c) glucose disappearance rates after insulin and glucose were 20% lower than in the control rats but the difference did not reach statistical significance. In conclusion, Zucker rats are much more sensitive to streptozotocin than Sprague-Dawley rats. In the Sprague-Dawley strain, a modest insulin deficiency is associated with insulin antagonism. Since these rats treated with low doses of streptozotocin are characterized by decreased glucose-induced insulin secretion and insulin antagonism, they may serve as an appropriate model for type 2 diabetes mellitus.

Animals↗
PubMedDate not supplied

Relationship between dipstick positive proteinuria and albumin:creatinine ratios.

Currently, neither the American Diabetes Association nor the Kidney Foundation consider the results of a positive dipstick urine test for protein, a semi-quantitative measurement, in the final evaluation of diabetic nephropathy. Instead, they require a quantitative test. The object of this study was to assess whether a positive semi-quantitative test could accurately substitute for a quantitative one to evaluate renal disease. We determined the proportion of urine samples dipstick positive for protein that had an albumin:creatinine ratio of 30 microg/mg or more, the recommended value for the diagnosis of microalbuminuria (incipient nephropathy). Albumin:creatinine ratios were measured in urine samples from 19 diabetic and 51 nondiabetic patients in which the dipstick test for protein was positive. Twelve of 24 (50%) urine samples trace positive for protein by a dipstick method had albumin:creatinine ratios of 30 microg/mg or more, whereas 42 of 46 (91%) urine samples greater than or equal to 1+ for protein exceeded that ratio. The results were similar in the two groups of patients. The positive predictive value for a test result more than or equal to 1+ for protein was 91%. We conclude that in contrast to the recommendations of the American Diabetes Association and the National Kidney Foundation, dipstick positive proteinuria of more than or equal to 1+ can substitute for an albumin:creatinine ratio. An algorithm for this more cost-effective approach to the diagnosis of diabetic nephropathy is suggested.

Albuminuria↗
PubMedDate not supplied

Effects of various enteral feeding products on postprandial blood glucose response in patients with type I diabetes.

These studies were performed to evaluate the postprandial blood glucose responses to a variety of differently formulated enteral feeding products in patients with type I diabetes. Eleven subjects with type I diabetes were evaluated in three studies, all using a Biostator (artificial endocrine pancreas) that delivered a small, basal amount of insulin and measured blood glucose levels. Subjects consumed 20 mL of the assigned formula every 15 minutes for the 240 minutes of the study. Study 1 evaluated the response to each of five products: Glucerna, Enrich, Ensure HN, Pulmocare, and Compleat Modified. When the postprandial blood glucose response to Glucerna was greater than when its research formulation (EN-8715) had been tested in 1988, studies 2 and 3 were undertaken to assess why this discrepancy occurred. Study 2 compared stored EN-8715 to Glucerna and study 3 compared frozen and thawed vs nonfrozen EN-8715, because of a concern that the original product had been frozen during shipping. In study 1 the glucose response (assessed as area under the glucose curve) correlated with the grams of carbohydrate present in the enteral feeding formula (r = .58, p = .002). The presence or absence of fiber, in the form of soy polysaccharide, did not affect the glucose response. Glucerna produced a significantly lower blood glucose response than did Enrich, Ensure HN, or Compleat Modified, although this response was greater than the response to EN-8715 in 1988. However, in study 2 no differences were found between stored EN-8715 and Glucerna and in study 3, freezing and thawing was not found to significantly alter the glucose response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Effect of a pharmacist-managed diabetes care program in a free medical clinic.

Diabetes care, morbidity, and mortality are usually worse in poor minority populations compared with non-minority ones. This report evaluates evidence-based process and outcome measures of diabetes care in diabetic patients followed in a free medical clinic and compares them to published results. The following process measures compared favorably with measures of the general population: dilated eye and foot exams and measurements of glycated hemoglobin levels; concentrations of total cholesterol; fasting triglycerides and low density lipoprotein (LDL) cholesterol; and proteinuria (by dipstick). Process and outcome measures in 89 diabetic patients referred to a Diabetes Management Program in which diabetes care was delivered by pharmacists following detailed algorithms (experimental group) were compared with measures in 92 diabetic patients who received diabetes care in the general clinic setting (control group). The patients in the experimental group had a slightly longer duration of diabetes and more microvascular and neuropathic complications, and more diabetic patients were taking insulin than were patients in the control group. All of the process measures listed above were more frequent in the experimental group. Compared with the control group, the initial glycated hemoglobin level (% +/- SE) in the experimental group was significantly (P < .001) higher (8.8 +/- 0.2 versus 7.9 +/- 0.2) but fell significantly (P < .03) more (-0.8 +/- 0.2 versus -0.05 +/- 0.3). The lack of a greater decrease in the glycated hemoglobin levels in the experimental group was not related to the inability of the pharmacists to follow the algorithms, the patients' refusal to follow the recommended medication adjustments, or the lack of appropriate self-monitoring of blood glucose in insulin-requiring patients. It was inversely related (r = -0.36, P < .03) to the number of missed visits, i.e., the greater the number of broken appointments, the less the glycated hemoglobin fell. In conclusion, diabetes care for a poor minority population in a free clinic setting can compare favorably to care in the general population. Pharmacists following detailed algorithms can enhance this care further. Administrative and support system changes that minimize the number of missed visits might further improve diabetes care in this population.

California↗
PubMedDate not supplied

Effects of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men.

Diabetes mellitus has been shown to develop as a consequence of chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition. Prior limited trials in humans had indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random crossover trial of inorganic Cr trichloride, a brewer's yeast that contained Cr as glucose tolerance factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 mo each. Subgroups included 21 ketosis-prone men; 7 ketosis-resistant, nonobese men; and 15 ketosis-resistant obese men. Chromium levels were followed pre- and posttreatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after i.v. tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments. Despite this lack of effect on carbohydrate levels, the ketosis-resistant subgroups demonstrated a significant increase in postprandial insulin after treatment with the brewer's yeast that contained GTF.

Blood Glucose↗
PubMedDate not supplied

Simple solution to problem of biostator-induced insulin aggregation.

It has recently been reported that there is a significant loss of insulin immunoreactivity and bioavailability secondary to heat-induced insulin aggregation during prolonged insulin delivery by the Biostator. This artifact of Biostator insulin delivery system makes data generated by studies that use prolonged, continuous insulin infusions performed with the Biostator uninterpretable. We report the prevention of this problem by the addition of 20 ml heparinized whole blood to a 500-ml reservoir containing the insulin to be infused. The proposed solution is simple, economical, and without risk to the subject since his or her own blood can be used.

Biological Availability↗
PubMedDate not supplied

Importance of control in type II diabetes mellitus.

OBJECTIVE: To determine the effect of maintenance of control of type II diabetes mellitus on the occurrence of complications. METHODS: Various published studies of populations of patients with diabetes are reviewed, and their results in terms of diabetic control and development of retinopathy, nephropathy, neuropathy, and macrovascular disease are summarized. RESULTS: Maintenance of near-euglycemia reduced the risk of worsening diabetic retinopathy; proliferative retinopathy developed in few patients with well-controlled diabetes. Similarly, worsening proteinuria was more common in patients with fair and poor control of diabetes in comparison with those who were able to maintain good control of diabetes. Furthermore, patients with poor diabetic control experienced a faster deterioration of peripheral neurologic function than did the patients with well-controlled diabetes. In five prospective studies of a total of 2,471 patients with type II diabetes, stricter control of diabetes was associated with fewer cardiovascular events and deaths. CONCLUSION: Overwhelming evidence from published prospective studies indicates that the complications often associated with type II diabetes can be minimized or delayed by maintaining good control of the disease.

Journal Article↗