Effects of long-term (2 months) supplementation of diet with 20 g of guar gum and 10 g of wheat bran on metabolic control was studied in 12 obese, poorly controlled noninsulin-dependent diabetic patients. Addition of fiber reduced urinary excretion of glucose from 30.5 +/- 6 to 8.3 +/- 2 g/24 h, (p less than 0.025), fasting plasma glucose concentration from 301 +/- 24 to 184 +/- 15 mg/dl (p less than 0.025), and plasma cholesterol concentration from 277 +/- 24 to 193 +/- 9 mg/dl (p less than 0.025). No significant changes were observed in the patients weight and serum concentrations of triglycerides, high-density lipoproteins, free fatty acids, and insulin. Addition of fiber also delayed gastric emptying of liquids and solids. This effect became statistically significant 60 and 90 min after intake of a test meal for liquids and solids, respectively. We conclude that addition of guar and bran to the diet resulted in long-term improvement of metabolic control in these patients and that delayed gastric emptying may be one of the mechanisms responsible for this beneficial effect.

When platelets were incubated with prostacyclin, prostaglandin E1, or prostaglandin D2 at concentrations insufficient to increase the level of adenosine 3',5'-monophosphate (cyclic AMP), coagulation factor X was activated by a platelet cysteine protease. Prostacyclin or prostaglandin E1 at higher concentrations increased the cyclic AMP level and inhibited the activation of factor X by platelets. Inhibition of platelet adenylate cyclase by 2',5'-dideoxyadenosine allowed the activation of the protease at higher concentrations of the autocoids. Prostaglandins A1, A2, B1, B2, E2, F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2, which do not affect platelet cyclic AMP level, did not stimulate the protease.

We have determined total body carbohydrate and lipid oxidation rates in response to a standard breakfast in nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in seven age- and weight-matched controls. The patients with NIDDM were studied twice, once while in poor glycemic control (fasting blood glucose concentration 267 +/- 24 mg/dl, urinary glucose excretion 28.9 +/- 6.3 g/24 h) and again after modest glycemic improvement following 2 mo of fiber treatment (fasting blood glucose 227 +/- 19 mg/dl, urinary glucose excretion 10.7 +/- 1.9 g/24 h). Basal carbohydrate (CHO) oxidation rates were normal in patients with NIDDM before and after fiber treatment. However, in patients before fiber treatment the rise in CHO oxidation rates, the reciprocal fall in lipid oxidation rates, and the rise in serum insulin and C-peptide concentrations after the breakfast were all severely blunted. In addition, storage of ingested CHO was significantly reduced (from 55% to 32%, P less than 0.05). After fiber treatment, postbreakfast CHO oxidation rates had improved and were no longer significantly lower than control values. In contrast, CHO storage remained suppressed. We conclude that (1) basal CHO oxidation remained normal but that postbreakfast CHO oxidation was impaired in our obese patients with NIDDM. This impairment, however, appeared to be a relatively late event, occurring only during severely uncontrolled NIDDM. (2) Inability to dispose of CHO by storage appeared to be an earlier defect with a greater impact on glucose tolerance than the impairment of CHO oxidation.

Metastases of various malignancies have been shown to be inversely related to the abundance of nm23 protein expression. However, the downstream pathways involved in nm23-mediated suppression of metastasis have not been elucidated. In the present investigation, we used cDNA microarrays to identify novel genes and functional pathways in nm23-mediated spontaneous breast metastasis. Microarray experiments were performed in a pair of cell lines, namely, C-100 (only vector transfected; highly metastatic) and H1-177 (nm23 transfected; low metastatic), derived from human mammary carcinoma cell line MDA-MB-435. The cDNA microarray analysis using GeneSpring software revealed significant as well as consistent alterations in the expression (up-and downregulation) of 2,158 genes in a total of 18,889 genes between high and low metastatic cells. Some of these genes were grouped into 6 functional categories, namely, invasion and metastasis, apoptosis and senescence, signal transduction molecules and transcription factors, cell cycle and repair, adhesion, and angiogenesis to extrapolate an association between these genes and different functional pathways involved in nm23-regulated metastasis. The results suggest that nm23 gene plays a major role in metastasis and its mechanism of action of metastasis suppression may involve downregulation of genes associated with cell adhesion, motility (integrins ␣2, -8, -9, -L and -V, collagen type VIII ␣1, fibronectin 1, catenin, TGF-␤2, FGF7, MMP14 and 16, ErbB2) and possibly certain tumor/metastasis suppressors (2 members of SWI/SNF-related matrix-associated proteins 2 and 5 and PTEN Reduced expression of nm23 gene (nonmetastatic gene) is related to high incidence of lymph node and distant metastasis and to poor prognosis of patients in several human malignant tumors. 1 In some other cancers such as prostate cancer, non-Hodgkin lymphomas and neuroblastoma, on the other hand, a high nm23-H1 expression is linked to an unfavorable outcome. 2 Recent studies have shown that in neuroblastoma, gain of 17q and activation of oncogene c-myc can upregulate nm23-H1 and -H2 and may confer a poor prognosis. 3 It is therefore possible that in these tumors, nm23 overexpression may be a consequence of a different oncogenic or an unknown mechanism. While conflicting results were observed in different solid tumors, nm23, however, is universally classified as a putative metastasis suppressor gene. The nm23 expression pattern appears to be the key to the differences observed between tumor cells of high and low metastatic potential. 1 Experimentally, it has also been demonstrated that nm23 may be involved in cellular functions leading to the metastatic phenotype, such as cell motility, which points to a regulatory role for nm23 proteins in cellular signaling pathways. 4 -6 While it has been shown that nm23 is involved in the suppression of metastasis, the exact mechanism by which it regulates metastasis remains to be elucidated. It is possible that nm23 activates or downregulates certain target genes involved...

We studied a patient with Acanthosis nigricans and the type B syndrome of severe insulin resistance. The patient's rates of basal glucose disappearance and appearance were both normal (2.2 and 1.7 mg/kg . min, respectively). FFA, betahydroxybutyrate, and acetoacetate concentrations were stable at 0.8, 1.0, and 0.3 mM, respectively, during a 2-h saline infusion after an overnight fast, indicating continued presence of insulin-like activity (ILA) in her serum. Infusion of insulin at rates of 2.7 and 27 U/h, raising peripheral insulin concentrations from 1400 to 4000 and 6000 microU/ml, respectively, had no effect on glucose disappearance and appearance or plasma concentrations of beta-hydroxybutyrate, acetoacetate, and FFA, suggesting that the observed ILA was not caused by the patient's plasma insulin. To determine the source of the ILA we used the patient's serum containing antiinsulin receptor antibodies (AIRA) to study its acute (2 h) and chronic (24 h) effects on insulin binding and glycogen synthesis in rat hepatocytes in primary culture. Preincubation of hepatocytes with AIRA serum (diluted 1:100) inhibited insulin binding by 84% and 88% after 2 and 24 h, respectively. It increased U-[14C]glucose incorporation into glycogen by 40% and 52% after 2 and 24 h, respectively. These effects were not caused by insulin present in the patient's serum. We conclude that AIRA serum, in addition to causing severe insulin resistance through inhibition of insulin binding, also exerted strong and long lasting insulin-like effects. These findings are compatible with the patient's clinical features of absence of ketoacidosis despite severe insulin resistance, decrease in glucose concentrations during fasting, and postprandial hyperglycemia.