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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are two different classes of humoral growth factors for arterial smooth muscle and endothelial cells that age of potential relevance for the development of macrovascular disease inn diabetes mellitus: hormones (growth hormone, insulin like growth factor I and II, insulin) and locally released growth factors of platelet origin. The following hormones have to be considered: Increased growth hormone plasma levels might contribute to macrovascular disease, but its actual relevance remains to be determined. Insulin like growth factor I and II are present in vivo and stimulate growth of vascular cells in vitro but their relevance for macrovascular disease in diabetes is unproven. To insulin, see Dr. Stout's paper. Human platelets contain at least six growth peptides or proteins that all stimulate in vitro growth of arterial wall cells: platelet derived growth factor, epidermal growth factor, platelet derived endothelial cell mitogen, endothelial growth factor, diabetic serum growth factor (DSGF), transforming growth factor-beta. As their plasma concentrations have not been shown to be increased in diabetes increased local availability at sites of stimulated platelet aggregation has been postulated. Therefore, their relevance for macrovascular disease i diabetics is based mainly on circumstantial evidence. The concentration of DSGF of platelet origin depends on the metabolic control: it increases in vivo in poorly controlled diabetics and is normalized after 2-3 weeks of good metabolic control in the same diabetic patient. The growth potency of DSGF from poorly controlled diabetics is greater than that of physiological amounts of insulin or growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular growth factors and the development of macrovascular disease in diabetes mellitus. 386 80

The effects of streptozotocin-induced diabetes on 125I-labeled epidermal growth factor (EGF) binding were studied in rat pancreatic acini. 125I-EGF binding was one-half maximal at 20 min, and maximal at 90 min. Saturation data revealed a decreased binding capacity in diabetic acini when compared with normal acini. Insulin, in vivo, normalized the decreased binding capacity. 125I-EGF internalization was also decreased in diabetic rat acini. Further, the inhibitory effect of cholecystokinin-octapeptide (CCK8) on cell-associated 125I-EGF radioactivity was significantly greater in diabetic than in normal rat acini. These findings suggest that insulin deficiency may lead to defective regulation of the exocrine pancreas by EGF.
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PMID:Epidermal growth factor binding is altered in pancreatic acini from diabetic rats. 609 11

It has been suggested that cellular transglutaminases may play an important role in the process of receptor-mediated endocytosis. We have examined this premise by investigating the receptor-mediated endocytosis of two proteins, epidermal growth factor and alpha 2 macroglobulin in cells that are deficient in transglutaminases. We find that endocytic activity is normal in these cells, ruling out an obligatory role for transglutaminases in endocytosis. We do find, however, that dansylcadaverine is not an inhibitor of endocytosis in cells that lack transglutaminase activity. Immunofluorescent localization of dansylcadaverine in dansylcadaverine-treated cells demonstrates incorporation of the amino into endocytic vesicles. We believe that covalent coupling of dansylcadaverine to cellular membranes may account for its ability to interfere with endocytosis in certain susceptible cells.
Diabetes Care
PMID:Studies on the effects of dansylcadaverine and related compounds on receptor-mediated endocytosis in cultured cells. 614 51

Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of vascular pathology in essential hypertension and diabetic macroangiopathy, whereas platelets constitute an important regulator of vessel wall homeostasis because of their content of various growth factors. Numerous abnormalities exist in platelet functions in diabetes and hypertension, such as enhanced activity and altered adhesion and aggregation. Increased thromboxane (TX2) production is characteristic of diabetes, and an elevation of intracellular free Ca2+ is found in platelets of hypertensive patients. By studying the growth patterns of VSMC from spontaneously hypertensive rats (SHRs) vs. those obtained from their normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that VSMC from SHRs exhibited a higher specific growth rate, abnormal contact inhibition, and accelerated entry into the S phase of the cell cycle. Moreover, they were hyperresponsive to many growth factors such as calf serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of hypertensive origin persist in culture indicating their putative primary role in the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented expression of its message levels in SHR VSMC, the difference in mRNA between both strains being more pronounced at high cell density. Further, TGF beta 1 protein synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of de novo labeled TGF beta 1. At high cell density, which most likely represents the physiological state of VSMC, plasmin, an activator of TGF beta 1, significantly stimulated DNA synthesis of VSMC in both strains. The reverse effect was obtained at low cell density. Yet, the fold stimulation was higher in WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This is supported by the inhibition of baseline DNA synthesis by TGF beta 1 neutralizing antibody in VSMC of hypertensive origin and not of normotensive controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the increased proliferation of SHR VSMC in culture. On the other hand, growth-promoting activity (GPA) in platelets of either diabetic or hypertensive patients was higher than in platelets of healthy controls and was found to be normalized by intensive insulin therapy in insulin-dependent diabetic patients. In hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25 mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Platelets, growth factors, and vascular smooth-muscle cells in hypertension and diabetes. 750 64

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.
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PMID:Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus. 776 95

Heparin binding epidermal growth factor (HB-EGF), a new member of the EGF family, is a potent mitogen for smooth muscle cells, fibroblasts, and mesangial cells. To study whether the HB-EGF is involved in the development of diabetic nephropathy, we measured the expression of the HB-EGF gene in the kidney tissues of streptozotocin-induced diabetic rats by Northern blot analysis. The mean kidney weight of diabetic rats without strict blood sugar control was significantly increased as compared to that of the control group. Renal HB-EGF mRNA expression was also increased in diabetic rats without strict blood sugar control at 7 days after induction of diabetes and remained elevated for the entire 3-month study period. Strict insulin treatment abolished the elevation of HB-EGF mRNA expression and kidney growth. As HB-EGF is a mitogen for mesangial cells, our results suggest that HB-EGF may be involved in the development of diabetic nephropathy.
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PMID:Increased expression of heparin binding epidermal growth-factor-like growth factor mRNA in the kidney of streptozotocin-induced diabetic rats. 785 68

In rodents, diabetes mellitus is accompanied by a decreased concentration of epidermal growth factor (EGF) in plasma and urine and by a reduced number of EGF receptors on the surface of target cells. A combination of these two abnormalities may reduce the effects of EGF and could be implicated in some complications of diabetes. The aim of the present work was to investigate the possible implication of the major source of EGF in the organism, the submandibular glands, upon the reduced EGF concentration in blood and urine. Firstly, we measured the content of mice submandibular gland EGF by radioimmunoassay and by morphometric determinations of the relative volume occupied by granular convoluted tubules in the gland and by the EGF-containing granules in the cells at the light and electron microscopical levels respectively. We found no differences in the EGF content of submandibular glands of streptozotocin-treated diabetic animals compared to control ones. Secondly, we estimated stimulus-secretion coupling by EGF-secreting cells, present in an enriched preparation of granular convoluted tubules (GCT) perifused in thermoregulated chambers. Phenylephrine was the only agent tested that was capable of stimulating EGF secretion. The stimulation was dose-dependent and similar in streptozotocin-diabetic and control mice. Thus, the EGF deficiency observed in diabetic mice is related neither to a defect of EGF content in the submandibular glands nor to an abnormal EGF secretion by the glands.
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PMID:Epidermal growth factor secretion by submandibular glands is not perturbed in the early phase of streptozotocin-induced diabetes in mice. 792 13

Experimental diabetes was induced in rats with streptozocin before mating, and the influence of diabetes on epidermal growth factor (EGF) in milk and on other milk components was studied. Throughout the lactation period, a significant decrease was found both in the production of milk and in the concentration of EGF in milk from untreated diabetic rats compared with an insulin-treated diabetic group and a control group. Thus, the total output of EGF in milk from diabetic rats was considerably decreased. The concentrations of total protein and haptocorrin, a cobalamin (vitamin B12)-binding protein, and the content of fat, however, were unaltered by diabetes. Therefore, the decrease in milk EGF seemed to be selective compared with total protein in milk. The pups of diabetic dams had reduced body weights within 1 wk of lactation and reduced body lengths on d 16 of lactation compared with control pups. Furthermore, the time of eyelid opening was delayed, but no difference in the time of tooth eruption was observed. Insulin-treatment of diabetic rats restored the milk volume and the EGF concentration to values comparable to those of the controls. Pups of the insulin-treated diabetic dams were comparable to the pups of the controls. These results indicate that insulin deficiency in lactating rats causes a decrease in the lactational performance and in the EGF content of milk.
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PMID:Decreased level of epidermal growth factor in milk from diabetic rats. 813 87

FSH in vitro stimulates increased oxygen uptake by isolated follicular granulosa cells from immature rats treated with diethylstilbestrol (DES) when substrates are present (glucose, glutamate, pyruvate or fumerate) or are completely absent. However, when glucose is the only substrate or when any single substrate is omitted from the buffer, FSH has no effect. FSH in vitro also increases the uptake of glucose and the formation of 14CO2 from [1-6 14C]-glucose. Granulosa cells from diabetic immature rats treated with DES did not show increased oxygen uptake with in vitro FSH. Diabetic cells had similar receptor binding of FSH to that of control non-diabetic cells. The addition of both insulin and FSH in vitro to buffer with diabetic granulosa cells gave increased oxygen uptake over that of control cells from diabetic rats. The insulin stimulation of oxygen uptake by FSH in cells from diabetic rats was not duplicated by either epidermal growth factor (EGF) or insulin-like growth factor I (IGF-1). Follicle counts of ovaries from diabetic and control immature rats treated with DES showed increased atresia in the diabetic ovaries after only 44 hr. of diabetes. Follicle counts of ovaries from adult diabetic rats showed increased atresia in 24 hours after induction of diabetes at proestrus. Follicle counts of pseudopregnant rats showed increased atresia by 3 days after diabetes was induced. We conclude that diabetes prevents normal follicle growth stimulated either by exogenous DES or by endogenous hormones secreted during proestrus.
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PMID:Diabetes prevents the normal responses of the ovary to FSH. 828 34

Studies characterizing actions of growth hormone (GH) and insulin-like growth factors (IGF) in kidneys of adult and developing animals and humans have provided a good deal of insight into the functions of these peptides. Although certain of the actions may be mediated directly by GH, most appear to result from effects of GH to increase levels of circulating IGF or IGF produced in kidney. In addition to GH, epidermal growth factor (EGF) enhances the renal synthesis of IGF-I. Enhancement of renal IGF-I expression is GH independent in compensatory hypertrophy. Stimulation of kidney IGF-I production also occurs in diabetes mellitus. Renal IGF-I production is elevated in these settings in the absence of changes in circulating IGF-I, consistent with a causative role of renal IGF-I for the accompanying increased glomerular filtration rate and kidney growth. Actions of IGF in kidney are initiated following binding of peptides to specific receptors. Receptor number may be altered during compensatory growth and in diabetes mellitus. In addition to IGF, several IGF binding proteins (IGFBP) are produced in kidney and are likely to both inhibit and enhance the actions of IGF in different circumstances through sequestration of peptides and regulation of peptide interactions with their receptors. Administration of IGF-I to rats following acute ischemic injury hastens the recovery of normal renal function and accelerates the regeneration of the damaged proximal tubular epithelium. IGF-I increases the glomerular filtration rate in humans with normal and reduced functional kidney mass. These findings establish the potential for use of this peptide as a therapeutic agent in the settings of acute and chronic renal failure.
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PMID:The growth hormone insulin-like growth factor axis in kidney revisited. 839 19


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