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Biomedical subjects

D M Rocha

Publications and source records attributed to D M Rocha.

9 recordsLinked to original sources
PubMed1999

Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.

Obesity is commonly associated with elevated plasma free fatty acid (FFA) levels, as well as with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors. What causes insulin resistance and hyperinsulinemia in obesity remains uncertain. Here, we have tested the hypothesis that FFAs are the link between obesity and insulin resistance/hyperinsulinemia and that, therefore, lowering of chronically elevated plasma FFA levels would improve insulin resistance/hyperinsulinemia and glucose tolerance in obese nondiabetic and diabetic subjects. Acipimox (250 mg), a long-acting antilipolytic drug, or placebo was given overnight (at 7:00 P.M., 1:00 A.M., 7:00 A.M.) to 9 lean control subjects, 13 obese nondiabetic subjects, 10 obese subjects with impaired glucose tolerance, and 11 patients with type 2 diabetes. Euglycemic-hyperinsulinemic clamps and oral glucose tolerance tests (75 g) were performed on separate mornings after overnight Acipimox or placebo treatment. In the three obese study groups, Acipimox lowered fasting levels of plasma FFAs (by 60-70%) and plasma insulin (by approximately 50%). Insulin-stimulated glucose uptake during euglycemic-hyperinsulinemic clamping was more than twofold higher after Acipimox than after placebo. Areas under the glucose and insulin curves during oral glucose tolerance testing were both approximately 30% lower after Acipimox administration than after placebo. We conclude that lowering of elevated plasma FFA levels can reduce insulin resistance/hyperinsulinemia and improve oral glucose tolerance in lean and obese nondiabetic subjects and in obese patients with type 2 diabetes.

Adult↗
PubMed1998

Mechanism of the diabetogenic action of cyclosporin A.

To investigate the mechanism of diabetogenic action of cyclosporin A (CsA), 7 male Wistar albino rats received 10 mg/kg/day of the drug for 4 weeks (CsA). The results were compared with controls (C); blood CsA levels measured weekly remained stable throughout the experiment (mean +/- SEM) (X = 2657.9+/-155.1 ng/ml). Intravenous glucose load (0.75 g/kg) performed after 2 weeks of CsA therapy showed glucose intolerance in treated animals as evaluated by the glucose area under the curve (CsA = 409.2+/-17.8 vs. C = 313.3+/-12.6 umol x ml(-1) x min(-1)) (p < 0.05) with insulin levels being similar in the two groups (CsA = 8603.9+/-1645.5 vs. C = 9571.9+/-828.5 pmol x ml(-1) x min(-1)). After 4 weeks of CsA administration, glucose intolerance was maintained (CsA = 398.6+/-35.6 vs. C = 301.7+/-23.0 umol x ml(-1) x min(-1)) (p < 0.05) associated with a significant decrease in insulin secretion (CsA = 4404.9+/-2392.0 vs. C = 10075.9+/-2861.0 pmol x ml(-1) x min(-1) (p < 0.05). These results suggest that CsA induced a state of insulin resistance preceding the failure of insulin secretion. After 4 weeks, the pancreatic insulin content was also decreased (CsA = 0.7+/-0.1 vs. C = 1.4+/-0.5 mU/mg) (p < 0.05). Maximal insulin binding to isolated adipocytes was not affected by CsA (CsA = 7.4+/-2.6 vs. C = 6.4+/-2.0%), although glucose transport and oxidation decreased after CsA treatment (p < 0.05). In conclusion, glucose intolerance induced by CsA in Wistar albino rats is due to decreased insulin production and impaired insulin action by a post-binding mechanism.

Adipocytes↗
PubMed1997

Insulin resistance in limb and trunk partial lipodystrophy (type 2 Köbberling-Dunnigan syndrome).

We studied insulin action in two patients with limb and trunk partial lipodystrophy with hirsutism and acanthosis nigricans. Glucose was normal in one of the patients and slightly above normal in the other during an oral glucose tolerance test (OGTT). An intravenous glucose tolerance test (IVGTT) was normal in both patients. Basal and glucose-stimulated insulin levels were elevated in both the OGTT and IVGTT in both patients. The response of plasma glucose to exogenously administered insulin was decreased. A euglycemic-hyperinsulinemic clamp performed in patient no. 2 indicated insulin resistance, which was not corrected by reducing the increased basal level of serum free fatty acids (FFAs). Binding of insulin to neck adipocytes was normal in both subjects, but glucose transport and oxidation in these cells was impaired. Insulin binding to abdominal adipocytes was increased in one patient whose adipocytes displayed higher glucose transport at low insulin concentrations. Glucose oxidation was decreased in abdominal adipocytes of both patients. We conclude that insulin resistance in Köbberling-Dunnigan type 2 partial lipodystrophy is not related to an alteration of the insulin molecule or to changes in insulin binding, but is more likely associated with a postreceptor defect, since glucose oxidation was impaired in adipocytes of the neck and abdomen.

Adult↗
PubMed1997

Human insulin allergy-immediate and late type III reactions in a long-standing IDDM patient.

UNLABELLED: Human insulin allergy-immediate or late type III reaction-is a rare event. We report the case of a 33-year-old female patient with insulin-dependent diabetes mellitus for 25 years who presented, in the last 8 years, mild but generalized urticaria partially controlled with oral antihistamines. There was no improvement after changing from mixed beef-pork to human insulin. In the last 3 years another allergic manifestation began: small, localized, subdermal and painful non-erythematous nodules with central hematomas at injection sites, occurring 6-8 h after the insulin injection and lasting for 48 h. The following maneuvers had no benefit: (1) Human insulin (NPH or Lente) administered with dexametasone or xylocain locally, (2) Short acting human insulin with or without previous boiling, (3) Anti-histamine cetirizine dihydrochloride-10 mg/day. The allergic symptoms disappeared only after treatment with short acting human insulin (up to 100 U/day) associated to prednisone-40 mg/day and cetirizine dihydrochloride for 4 months. However, after stopping prednisone the urticaria reappeared and it was relieved with insulin desensitization. The pain at the site of injections persisted. CONCLUSION: This long-standing IDDM patient presented two types of reactions to human insulin: the immediate type (systemic urticaria), treated with antihistamines and desensitization, and the Arthus' type III reaction (nodules and hematomas occurring 6-8 h after the insulin injection) that required glucocorticoid therapy for more than 4 months.

Adult↗
PubMed1993

Metabolic derangements in excessive insulin and sulfonylurea therapy.

Mild streptozotocin diabetic rats, characterized by normal or slightly elevated fasting blood glucose levels and glucose intolerance, treated with excessive doses of monocomponent pork insulin (0.5 U/day) (I) or glybenclamide (0.6 mg/day) (S) were compared to controls (C) and streptozotocin-diabetic rats without treatment (D). Intravenous glucose tolerance tests (0.75 g/kg) were performed in all animals and repeated after overtreatment. Insulin binding and insulin-induced D-(U-14C)-glucose transport and oxidation were also determined in isolated epididymal adipocytes. Diabetic rats showed a failure in the initial phase of insulin release and glucose intolerance as compared with (C). In overtreated rats glucose tolerance worsened (p < 0.05) after therapy. Maximal insulin binding by isolated adipocytes at tracer insulin concentration was unchanged after excessive insulin or sulfonylurea therapy. Besides, glucose transport and oxidation in the cells of overtreated rats were greater than in D and even greater than in C. These apparently divergent results, i.e. deterioration of glucose tolerance with increased insulin action in adipocytes suggest that overtreatment induces a state of resistance to hormone action in other target tissue(s) than the adipose one, possibly muscle.

Adipocytes↗
PubMed1993

Ultrasonographic abnormalities of the pancreas in IDDM and NIDDM patients.

OBJECTIVE: To evaluate the relationship between the type and duration of diabetes and pancreas size by ultrasonography. RESEARCH DESIGN AND METHODS: Pancreas images of 40 IDDM and 36 NIDDM patients with 0.3-34 yr of disease were compared with those of 60 normal healthy control subjects. RESULTS: The diameters +/- SD of the head, body, and tail of the pancreas in IDDM patients (1.9 +/- 0.3; 0.9 +/- 0.2; and 1.4 +/- 0.2 cm, respectively) were smaller than in NIDDM patients (2.7 +/- 0.4; 1.2 +/- 0.3; and 1.8 +/- 0.4 cm, respectively) and control group subjects (2.4 +/- 0.4; 1.1 +/- 0.3; and 1.8 +/- 0.4 cm, respectively). The pancreatic shrinkage in IDDM patients was clearly evident after 10 yr of the disease. NIDDM patients and control subjects had similar pancreatic dimensions, except for a greater body thickness in NIDDM patients with > 10 yr of disease (1.2 +/- 0.4 vs. 1.1 +/- 0.3 cm). These results were not related to differences in age, sex, and body size. Pancreas image was hypoechogenic in 72.5% of IDDM patients and hyperechogenic in 83.3% of NIDDM patients. CONCLUSIONS: Smaller pancreases in IDDM patients in comparison with NIDDM patients and control subjects were clearly demonstrated only after 10 yr of disease. Patients with NIDDM were not affected by pancreatic dimensions, except for a greater body thickness after 10 yr of disease. Pancreatic echogenicity increased with age.

Adult↗
PubMed1972

Glucagon-stimulating activity of 20 amino acids in dogs.

The effect of 20 L-amino acids upon pancreatic glucagon secretion has been studied in conscious dogs. Each amino acid was administered intravenously over a 15 min period in a dose of 1 mmole/kg of body weight to a group of four or five dogs. Pancreatic glucagon and insulin were measured by radioimmunoassay. 17 of the 20 amino acids caused a substantial increase in plasma glucagon. Asparagine had the most glucagon-stimulating activity (GSA), followed by glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine, glutamate, threonine, glutamine, arginine, ornithine, proline, methionine, lysine, and histidine. Only valine, leucine, and isoleucine failed to stimulate glucagon secretion, and isoleucine may have reduced it. No relationship between glucagon-stimulating activity and insulin-stimulating activity was observed. The amino acids which enter the gluconeogenic pathway as pyruvate and, which are believed to provide most of the amino acid-derived glucose, had a significantly greater GSA than the amino acids which enter as succinyl CoA or as alpha-ketoglutarate. However, pyruvate itself did not stimulate glucagon secretion. The R-chain structure of the amino acid did not appear to be related to its GSA, except that the aliphatic branched chain amino acids, valine, leucine, and isoleucine, were devoid of GSA.

Amino Acids↗