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M N Feinglos

Publications and source records attributed to M N Feinglos.

At least 55 records · Page 3Linked to original sources
PubMed1987

Failure of genetically selected miniature swine to model NIDDM.

Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic diet; and 4 mo of excess diabetogenic diet for obesification. Results of oral glucose tolerance and intravenous insulin tolerance tests conducted at the end of each regimen were compared. Hyperglycemia was not observed in any animals after any manipulation. Insulin sensitivity was also not influenced by diet. We conclude that F7 low-K miniature swine from this colony fail to model human non-insulin-dependent diabetes.

Animals↗
PubMed1986

The intravenous insulin tolerance test in type I diabetes.

The intravenous insulin tolerance test (ITT) allows general assessment of insulin sensitivity by determining the fall in plasma glucose after injection of 0.1 unit/kg regular insulin. To evaluate the usefulness of this test diagnostically in distinguishing Type I from Type II diabetes, 24 patients with Type I diabetes (defined as early age of onset, ideal body weight or less at onset, and insulin dependence) underwent ITTs. Seven patients had normal glucose disposal rates (Ki greater than or equal to 2.5. Nine patients had Ki less than 2.5 but greater than 1.0. Eight patients had Ki less than 1.0. The slopes did not correlate with the control of the diabetes (as assessed by measurement of glycosylated hemoglobin), the presence or titer of anti-insulin antibodies, the duration of the diabetes, the age of onset, the presence of complications, or the current insulin dose. These results indicate that varying amounts of insulin resistance may be present in Type I diabetes and cannot necessarily be explained by poor control or the presence of insulin antibodies.

Adolescent↗
PubMed1984

Behavioral manipulation of the diabetic phenotype in ob/ob mice.

The genetically obese mouse (C57BL/6J ob/ob) is a commonly used model of non-insulin-dependent diabetes mellitus. However, our studies demonstrate that, while the animal is significantly hyperinsulinemic, it in fact does not show consistent hyperglycemia in the resting state. During stress, both obese animals and their lean littermates become hyperglycemic, but the magnitude of the hyperglycemia is exaggerated in the obese mice. Obese animals also show an exaggerated plasma glucose increase in response to epinephrine injection. This increase in plasma glucose is accompanied by a decrease in plasma insulin in response to both stress and epinephrine. Our findings suggest that environmental stimuli influence the expression of diabetes in the C57BL/6J obese mouse and therefore must be considered in studies of this animal model of diabetes.

Animals↗
PubMed1983

Mechanism of action of the second-generation sulfonylurea glipizide.

Glipizide, a second-generation sulfonylurea, has potent antidiabetic actions in patients with noninsulin-dependent diabetes mellitus. The effects of glipizide treatment on insulin sensitivity, glucose-mediated insulin secretion, and glucose utilization were measured in newly diagnosed or untreated patients with noninsulin-dependent diabetes mellitus. The data indicate that the antidiabetic action of glipizide is primarily mediated by a potentiation of insulin action and, to a less significant and more variable degree, by an increase in nutrient-mediated insulin secretion. Studies in normal mice and dogs show that glipizide potentiation of insulin action is associated with an increase in plasma membrane insulin receptor number, involves some postreceptor events, and is significantly greater on peripheral uptake of glucose than suppression of hepatic glucose production. The initial event in glipizide action on beta cells appears to be binding to a specific plasma membrane receptor.

Animals↗
PubMed1983

Long-term safety and efficacy of glipizide.

We studied the effect of long-term glipizide therapy in a small group of closely monitored patients. Fasting plasma glucose, glucose tolerance, glucose-stimulated insulin secretion, and insulin sensitivity were measured on multiple occasions throughout the investigation. Our observations show that glipizide therapy is effective in certain patients with noninsulin-dependent diabetes mellitus over a prolonged time period. The major effect of the drug appears to be mediated by its alteration of insulin sensitivity, but glipizide also causes a sustained increase in glucose-stimulated insulin secretion in most patients.

Blood Glucose↗
PubMed1980

Therapy of insulin-independent diabetes mellitus: general considerations.

Rational approaches to the therapy of patients with insulin-independent diabetes should be based on correcting the underlying defects. The major metabolic abnormalities present in patients with insulin-independent diabetes are: (1) impaired insulin action, (2) defective glucose-mediated insulin secretion, and (3) hyperglucagonemia. All of these defects could be due to a generalized plasma membrane abnormality that affects insulin and glucose receptors or to a generalized disturbance in postreceptor insulin action. Insulin action may be increased by sulfonylureas, possibly by alterations in intracellular cyclic AMP content, or by weight-reducing diets. Insulin secretion may be increased by gastrointestinal hormones, sulfonylureas, serotonin antagonists, or weight-reducing diets. Individual patients with insulin-independent diabetes have varying degrees of insulin resistance or impaired glucose-mediated insulin secretion. The use of therapeutic agents to correct the predominant defect should provide the most effective means of controlling the hyperglycemia and glucose intolerance of the individual patient.

Blood Glucose↗
PubMed1980

Sulfonylurea treatment of insulin-independent diabetes mellitus.

The ultimate clinical utility of the sulfonylurea drugs in the treatment of insulin-independent diabetes mellitus will be determined only when the mechanisms of action of these agents are understood. We are presently evaluating the long-term effects of the sulfonylurea glipizide on a group of patients with insulin-independent diabetes. Our studies thus far indicate that a major effect of this drug is a potentiation of insulin action, which leads to an improvement in glucose utilization. However, glipizide, in distinction from those sulfonylureas that have been examined previously, also causes a long-term increase in glucose-stimulated insulin secretion. These effects are unrelated to diet therapy and can still be demonstrated in patients treated for more than 2 yr. Further investigation will determine whether sulfonylurea therapy can offer unique benefits to certain patients with insulin-independent diabetes.

Blood Glucose↗
PubMed1979

"Insulin" allergy due to zinc.

An investigation of two unrelated patients who had local cutaneous hypersensitivity reactions after injection of any commercially available insulin preparation has shown that the cause of the allergy was zinc. Zinc-insulin and zinc sulphate induced transformation and proliferation of peripheral-blood lymphocytes from these patients; they also induced the production of a specific leucocyte inhibitory factor. Intradermal skin-tests for zinc were positive in both patients. Similar studies carried out in a patient whose cutaneous allergy to insulin was corrected by changing from mixed beef-pork to pure pork insulin were negative. Zinc-free insulin did not produce any allergy in the first patients. The number of patients in whom zinc (which is present in all commercially available insulin preparations) is a cause of "insulin" allergy is unknown. These patients may by identified by intradermal skin-tests. This previously unrecognised allergy should be considered in all patients whose insulin allergy does not respond to conventional therapy.

Cell Migration Inhibition↗
PubMed1979

Sulfonylurea drugs and insulin-independent diabetes mellitus.

Insulin-independent diabetes is a disease characterized by insulin resistance and the patient's concomitant inability to compensate by exaggerated insulin secretion. A primary abnormality in the plasma membrane of the afflicted cells may cause both of these phenomena. Recent studies investigating the mechanism of action of sulfonylurea drugs show that these agents probably exert their antidiabetic action by increasing insulin sensitivity and ameliorating the insulin resistance, rather than by increasing insulin secretion. Dietary treatment alone, though effective in lowering the FPG level, does not ameliorate the insulin resistance of insulin-independent diabetes mellitus. Thus, sulfonylurea drugs appear to be rational therapeutic agents for the treatment of this form of diabetes. Clinical studies confirm the beneficial effects of these drugs in controlling the hyperglycemia of insulin-independent diabetes. Major unresolved questions are (1) Why do primary and secondary failures occur? (2) Is the underlying membrane abnormality progressive? (3) How long are sulfonylureas effective? (4) What is the mechanism of the membrane disturbance and how do sulfonylureas ameliorate it? (5) Do sulfonylureas drugs cause cardiovascular toxicity? The answers to these questions will provide further insight into our understanding of insulin-independent diabetes and will lead to the development of better drugs for its treatment. In the meantime, sulfonylureas are rational agents for the therapy for this disorder, if they are used appropriately.

Adult↗
PubMed1978

Measurement of plasma adenosine 3',5'-monophosphate.

Currently used methods for plasma cAMP measurements are either tedious (chromatographic preparation of sample) or potentially inaccurate (direct assay of plasma samples). A rapid, simple, and accurate competitive binding assay for plasma cAMP, which does not require chromatographic preparation of the sample, has been developed. This procedure prevents destruction of plasma cAMP by utilizing both theophylline and EDTA in the collection of the blood sample. Human plasma contains variable amounts of cAMP-binding activity which interfere with the measurement of cAMP by the standard competitive binding assay. Our assay procedure removes this binding activity by precipitation of plasma proteins with perchloric acid. The normal fasting value (+/- SD) of plasma cAMP using this technique is 17.6 +/- 4.3 pmol/ml, which is identical to values obtained by methods utilizing chromatographic purification of samples (18.3 +/- 3.0). The fasting plasma cAMP of patients with hyperparathyroidism is normal (16.2 +/- 3.4), but patients with maturity-onset diabetes mellitus have fasting values significantly below normal (12.3 +/- 2.4).

Animals↗
PubMed1977

Osteomalacia due to 1alpha,25-dihydroxycholecalciferol deficiency. Association with a giant cell tumor of bone.

Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yr-old woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27+/-1 ng/ml). However, the serum concentration of 1alpha,25-dihydroxycholecalciferol was low (1.6+/-0.1 ng/100 ml). Oral administration of physiological amounts of 1alpha,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities of the syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of 1alpha,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.

Adult↗
PubMed1977

Potentiation of insulin action: a probable mechanism for the anti-diabetic action of sulfonylurea drugs.

Insulin action was assessed by measuring insulin-mediated glucose disposal (KI) in 13 non-ketotic diabetic patients both before treatment and after normalization of plasma glucose by diet (5 patients) or sulfonylurea (glipizide) therapy (8 patients). While the KI of the diet-treated group was unchanged by therapy, that of the glipizide-treated group was significantly increased. The data show that chronic glipizide therapy is associated with a potentiation of insulin action, which may account for the major anti-diabetic effect of this drug.

Adult↗