Effects of the treatment with acarbose in elderly overweight type 2 diabetic patients in poor glycemic control with oral hypoglycemic agents or insulin.

The aim of this study was to evaluate the efficacy of acarbose, an inhibitor of alpha-glucosidase, on glycemic control in elderly overweight type 2 diabetic patients poorly controlled by oral hypoglycemic agents (OHA) or insulin. Our study included 22 overweight patients, 60-75-years-old, treated with OHA and/or insulin who, after a period of 4 weeks of controlled diet, showed a poor metabolic control. They were divided into two groups: Group I (nine patients) on OHA treatment; Group II (13 patients) undergoing treatment with insulin alone or in combination with OHA. Acarbose was administered to all the patients (100 mg three times a day at meal times) for 6 months in addition to their previous treatment. The addition of acarbose caused a significant reduction in both groups with regard to fasting glycemia (after 3 and 6 months, respectively, 20.7 and 21.9%, P<0.04 in Group I; 19.1 and 21.8%, P<0.04 in Group II), and postprandial glycemia (after 3 and 6 months, respectively, 41.6 and 42.5%, P<0.0001 in Group I; 35.6 and 38%, P<0.0006 in Group II). There was also a significant reduction in the values of HBA(1c) in Group I after 6 months of treatment (24.3%, P<0.05) and in Group II after 3 and 6 months (respectively 13.4%, P<0.02 and 20.6%, P<0.01). Three months after treatment with acarbose ended, fasting and postprandial glycemia and HBA(1c) values returned to original baseline values. In conclusion, the addition of acarbose to the OHA in elderly overweight type 2 diabetic patients poorly controlled by OHA or insulin regimes improved metabolic control.

Deoxyspergualin neither counteracts lipopolysaccharide (LPS) or Staphylococcus aureus enterotoxin-B (SEB) induced lethality in mice nor does it modulate the release of tumor necrosis factor-alpha.

To gain further insights into the immunopharmacological mode of action of the immunosuppressant antibiotic deoxyspergualin (DSP), its effects were evaluated in murine lethal endo- and exotoxemia. These are two cytokine-mediated macrophage and T cell dependent immunoinflammatory conditions that can be induced in D-Galactosamine (D-Gal) presensitized mice by the injections with either LPS or SEB, respectively. The results show that prophylactic treatment with DSP (2.5 or 5 mg/kg bd.wt. 48, 24 and 2 h prior to challenge) neither improved the rate of survival, nor influenced the massive increase in the blood levels of tumor necrosis factor-alpha which followed the challenge with LPS or SEB. In sharp contrast, these clinical and seroimmunological events were both markedly counteracted by prophylactic treatment with sodium fusidate, another immunosuppressive agent used as control.

[Comparative study of the efficiency of ultralente insulin and NPH insulin combined with sulfonylurea in type 2 diabetes patients with secondary tolerance to sulfonylurea. Possible selection criteria]. / Studio comparato tra l'efficacia dell'insulina ultralenta e dell'insulina NPH in associazione alle sulfoniluree in pazienti diabetici di tipo 2 con fallimento secondario alle sulfoniluree. Possibili criteri di scelta.

The treatment of NIDDM patients with secondary failure to sulfonylureas is still a debated problem. In this study we compared in NIDDM patients with secondary failure to glyburide, the effect of adding a single, low-dose bed time either NPH or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective sulfonylurea treatment. Both NPH and ultralent insulin therapy have been demonstrated to be effective in ameliorating metabolic control in NIDDM patients with secondary failure to sulfonylureas. However, the addition of bed-time ultralent insulin caused a greater and significant decrease in post prandial plasma glucose. In contrast, the average fasting plasma glucose decrease was significantly greater after NPH insulin administration. These results indicate that in NIDDM patients with secondary failure to glyburide bed-time ultralent insulin administration is a better tool to improve the post prandial plasma glucose.

Evidence that two naturally occurring human insulin receptor alpha-subunit variants are immunologically distinct.

The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I-labeled insulin to various cells or tissues (placenta, IM-9, adipocytes, HEp-2-larynx cells, Epstein-Barr virus lymphocytes) but not greater than 50% of 125I-labeled insulin binding to human liver membranes. Conversely, both the IgG fraction from this patient, which did not bind protein A (flow-through IgG [IgGb]), and the IgGa fraction from a second similar patient (Italy 1 [I-1]) almost completely inhibited the binding of 125I-labeled insulin to liver membranes. The IgGa fraction from patient I-2 did not change receptor affinity because 50% inhibition of 125I-labeled insulin binding was not affected by either the presence or absence of these IgG fractions. Furthermore, liver binding data were not due to cross-reaction of 125I-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on 125I-labeled insulin binding to liver. Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited 125I-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of insulin secretion by diazepam binding inhibitor and its processing products.

The effect of purified rat brain diazepam binding inhibitor (DBI) and that of synthetic DBI fragments DBI33-50 [octadecaneuropeptide (ODN)], DBI17-50 [triakontatetraneuropeptide (TTN)], DBI42-50 and DBI53-62 were studied on glucose-induced secretion of insulin from isolated rat pancreatic islets in both static incubation and perifusion experiments. DBI and ODN did not affect the secretion of insulin in the presence of 2.8 mM glucose (basal condition) but reduced the release of insulin induced by 16.7 mM glucose. The effects of DBI and ODN were significant at concentrations as small as 1-10 nM. In contrast, 100 nM TTN, DBI42-50 (which corresponds to the COOH-terminal region of ODN) and DBI53-62 (which corresponds to a region of DBI that is conserved among species), were without effect on both basal and 16.7 mM glucose-stimulated insulin secretion. DBI has previously been localized to the delta cells of islets of Langerhans (Ostenson, Ahren, Karlsson, Sandberg and Efendic, 1990) and the presence of DBI- and ODN-like immunoreactivity in isolated rat pancreatic islets has now been demonstrated. These results suggest that DBI and some of its processing products (ODN) may modulate glucose-stimulated secretion of insulin through a paracrine mechanism.

The stimulation of prolactin secretion by sulpiride in "adolescent gynaecomastia".

In order to evaluate the function of the hypothalamic-pituitary-prolactin axis in "adolescent gynaecomastia" (AG), sulpiride was administered to 7 normal boys and 7 boys with AG. The maximum increase in serum prolactin (PRL) above the mean baseline level (deltamax) was used as index of response. The sulpiride induced a greater PRL release in boys with gynaecomastia than in the controls. Our data indicate that boys with gynaecomastia may have a greater pituitary prolactin pool. The results also illustrate the usefulness of specific neurotrophic agents such as sulpiride as important tools for evaluating the function of the hypothalamic-pituitary-PRL axis.