Sociedade Brasileira de Diabetes

Filiada à International Diabetes Federation(IDF), a Sociedade Brasileira de Diabetes(SBD), é uma associação civil, sem fins lucrativos, com número ilimitado de sócios, fundada em dezembro de 1970. Tem como membros, médicos e profissionais de saúde com interesse em diabetes mellitus.

From insulin and insulin-like activity to the insulin superfamily of growth-promoting peptides: a 20th-century odyssey.

In 1941, Gellhorn reported that administration of human blood to hypophysectomized/adrenodemedullated rats caused a fall in blood sugar. This was among the early demonstrations that human blood possesses glucose-lowering or insulin-like activity (ILA). Gellhorn assumed he had detected only insulin. During the 1960s, however, it became evident that plasma ILA contained at least two components: one, suppressible ILA (SILA), was inactivated by anti-insulin antibody and was therefore considered to be indistinguishable from pancreatic insulin; the other, nonsuppressible ILA (NSILA), was unaffected by anti-insulin antibody. Subsequent work resolved NSILA into insulin-like growth factors I and II (IGF-I and IGF-II), two 7.5 kilodalton peptides with potent mitogenic properties; established their identity with the somatomedins; and investigated both their therapeutic potential and role in the pathogenesis of neoplastic and other human diseases. Insulin and the IGFs exhibit striking homologies in amino acid composition and some degree of overlap in their signaling pathways and actions. Moreover, insulin-like proteins have been identified not only in all vertebrate classes but also in molluscs, insects, and worms. These observations are the basis for the hypothesis that the genes encoding vertebrate insulins and IGFs and invertebrate insulin-like molecules evolved from a common ancestral gene, and for the concept of an insulin superfamily of growth-promoting peptides.

[Extrapancreatic hypoglycemic tumors. Apropos of a case of pleural fibrosarcoma]. / Tumeurs hypoglycémiantes extra-pancréatiques. Etude à propos d'un cas de fibrosarcome pleural.

The authors report a case of pleural fibrosarcoma associated with severe hypoglycaemia. Chromatography of the patient's serum and tumour fragments revealed a substance with a high molecular weight and an insulin-like activity. Professor Poffengarger's laboratory identified this substance as Non Suppressible Insulin-Like Protein or NSILAp which induces insulin-like effects on various tissues. A review of the literature is presented in the light of this case.

Insulin-like growth factor II and nonsuppressible insulin-like activity levels in newborns.

We measured insulin-like growth factor II and nonsuppressible insulin-like activity levels in the sera of newborn infants with different birth weights and gestational ages to determine the significance of these peptides in fetal growth. Our results obtained by use of one-way analysis of variance showed that the insulin-like growth factor II and nonsuppressible insulin-like activity levels in premature, average-weight-for-gestational-age, large-for-gestational-age, and small-for-gestational-age newborns were significantly different (p less than 0.01). Although levels in the premature neonates were less than the other three groups and large-for-gestational-age neonates had a higher insulin-like growth factor II level than the other three groups, maternal insulin-like growth factor II levels in all groups were similar. These results suggest that insulin-like growth factor II may play a major role in fetal growth.

Hypoglycemia in patients with non-islet cell tumors.

Persistent hypoglycemia occasionally is associated with tumors of many types. Usually these tumors are of large size and often are of mesenchymal origin. There is evidence of increased glucose uptake from the blood, some of which may occur in the tumor itself. In addition, hepatic glucose production may also be impaired. While increased levels of insulin have never been unequivocally established in the plasma of these patients, a number of insulin-like peptides have been reported. One such peptide may be related to insulin-like growth factor II, but reports from different laboratories are conflicting. Recently, the possible role of oncogenes in stimulating tumor glucose metabolism and tissue necrosis factor and other cytokines in stimulating general glucose uptake have received attention. Treatment of the condition includes surgery, radiation, or chemotherapy directed at the primary tumor and supportive measures with increased glucose administration and corticosteroids.

Insulina em invertebrados / Insulin in invertebrates

Este artigo reúne referências ao estudo de insulina e de substância insulina-símile em invertebrados publicadas na última década, constituindo-se numa revisäo de interesse para os que se dedicam ao ensino e à pesquisa na área de ciências biológicas. Analisa as metodologias utilizadas pelos diversos autores, os achados em protistas, procariotos e eucariotos e os conceitos admitidos em relaçäo à funcionalidade das estruturas estudadas

Growth hormone, somatomedin C, and nonsuppressible insulin-like activity levels compared in premature, small, average birth weight, and large infants.

We have investigated the relationship between growth hormone, somatomedin C, nonsuppressible insulin-like activity, weight, gestational age, and 1-minute Apgar score in newborn infants. The 153 infants were categorized as small for gestational age (n = 19), average for gestational age (n = 59), large for gestational age (n = 60), and premature (gestational age at birth, 36 weeks or less (n = 15). Our study showed that (1) growth hormone levels were elevated in premature infants and correlated with Apgar scores and birth weights; (2) somatomedin C and nonsuppressible insulin-like activity levels were significantly lower in premature than in term infants; and (3) the birth weight of all infants studied had a significant overall effect on both somatomedin C and nonsuppressible insulin-like activity levels, suggesting that these factors may be involved in fetal growth. However, because in small for gestational age infants somatomedin C and nonsuppressible insulin-like activity were similar to levels in average for gestational age infants, it is suggested that other factors may inhibit fetal growth.

Preferential association of the insulin-like growth factors I and II with metabolically inactive and active carrier-bound complexes in serum.

Ion-exchange chromatography of serum on DEAE-Sephadex A-50 using a stepwise NaCl gradient showed that complexes enriched with insulin-like growth factors I and II (IGF-I and IGF-II) could be preferentially eluted. A fraction eluted with 0.075 M-NaCl preferentially contained immunoreactive IGF-I with peak levels appearing in fractions of Mr approx. 110,000. The IGF-I-binding protein complex itself had low bioactivity as measured in a non-suppressible insulin-like (NSILA) bioassay. On conversion to free IGF-I by gel-permeation chromatography on Sephadex G-75 in 1% formic acid, however, the IGF-I did express its intrinsic NSILA bioactivity. In contrast, an IGF-II-enriched complex was eluted from the DEAE-Sephadex with 0.15 M-NaCl. Practically all of the recovered NSILA of the original serum was present in this fraction, in the Mr range 70,000-300,000 with a peak of 150,000. Chromatography on Sephadex G-75 in 1% formic acid separated this high-Mr NSILA into low-Mr (less than 15000) IGF-II and high-Mr acid-stable NSILA-P. The high-Mr IGF-II complex bound to concanavalin A-Sepharose, suggesting that it was a glycoprotein. The results confirm previous reports that a large portion of the NSILA of whole serum can be accounted for by a biologically active acid-dissociable complex. These data show for the first time that this active complex consists of an IGF-II-preferring binding protein. In direct contrast, the IGF-I-preferring complex does not express NSILA bioactivity until the IGF-I is liberated through acidification. The presence of a metabolically active IGF-II complex in serum raises questions as to its possible biological role in the adult.

Similarities between the insulin-like stimulatory effect of human IgG and NSILP.

Since the insulin-like stimulatory effect of human IgG on adipocyte lipogenesis, exerted through its Fc moiety, is not neutralized by anti-insulin antisera, IgG may contribute significantly to the non-suppressible insulin-like activity (NSILA) of plasma. 91% of NSILA has been shown previously to be associated with a high mol. wt. protein (NSILP). The purpose of this investigation was to assess whether IgG and NSILP have similar stimulatory effects on adipocyte lipogenesis and whether this effect can be neutralized by preincubation with gamma-chain specific anti-IgG antiserum; whether IgG stimulates 35S-sulphate uptake by porcine cartilage, known to be stimulated by insulin-like growth factors but not NSILP; and whether gamma-chain specific anti-IgG antisera precipitate IgG in a fashion similar to that with IgG preparations. Our investigations show that both IgG and NSILP have similar dose response relationships with respect to the stimulation of adipocyte lipogenesis and that both lose their adipocyte stimulating effect following preincubation with anti-IgG antiserum; neither IgG nor NSILP stimulate 35S-sulphate uptake by porcine cartilage, unlike serum somatomedin and crude NSILA-s preparations; and that gamma-chain specific anti-IgG antisera form precipitin lines with NSILP. Therefore, NSILP and IgG molecules have immunological and biological similarities; there may occur a homology between the Fc fragment of IgG and the NSILP molecule.