Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Continuous topical application of epidermal growth factor (EGF) to granulation tissue increases the rate of collagen accumulation. It is believed that the clinical use of growth factors, such as EGF, may become common in the treatment of impaired wound healing in the near future. Impairments in the production and degradation of wound collagens have been demonstrated in diabetes mellitus. We studied the effects of a single, local application of EGF on collagen content, collagenase activity, and the ratio of type III and type I collagens within granulation tissue using polytetrafluoroethylene (PTFE) wound cylinders in 48 streptozotocin-induced diabetic rats in order to determine potential benefits of EGF to wound healing in diabetics. Wound collagen content in EGF-treated diabetic animals was significantly higher than in diabetic controls during the first 10 days of wound healing (236% on day 5, P less than .001; 140% on day 10, P less than .01), but decreased to significantly lower levels by day 15 of healing (71% of diabetic controls, P less than .01; 47% of nondiabetic controls, P less than .01). An 18% increase in diabetic wound protease activity was observed following application of EGF (P less than .001). The ratio of type III collagen to total wound collagen within the granulation tissue was significantly reduced (P less than .001) following EGF application. We demonstrate that a single, topical application of EGF promotes early synthesis of type I collagen, thereby deranging the usual type III/total collagen ratio, and is associated with increased wound protease activity.
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PMID:EGF increases short-term type I collagen accumulation during wound healing in diabetic rats. 216 27

Serum very low molecular weight growth factor like-activity (S-VLMGA, molecular weight less than 3,000) and serum and urinary epidermal growth factor (S-, U-EGF) were investigated in 180 patients of non-insulin-dependent diabetes mellitus (NIDDM) by bioassay using skin fibroblast cells (CCD-27 SK) and enzyme- and radio-immunoassay, respectively. S-VLMGA was slightly elevated in NIDDM patients with retinopathy (RET) and/or neuropathy (NEU), but slightly decreased in those with nephropathy (NEP) compared with patients without complications, though the differences were not significant (without complications: 122 +/- 9, with RET and/or NEU and without NEP: 145 +/- 15, all with NEP: 110 +/- 8% of increased growth activity, mean +/- SE). The similar tendencies were seen in S- and U-EGF in the same groups. However the changes in S-EGF were small and the decrease of U-EGF in patients with NEP was remarkable (U-EGF of without complications: 22.7 +/- 2.5, with RET and/or NEU and without NEP: 24.5 +/- 4.2, all with NEP: 17.6 +/- 3.2 ng/mg creatinine, mean +/- SE). Furthermore, S-VLMGA was inversely, but U-EGF was positively related with the creatinine urinary vs serum ratio. Thus the concentrations of VLMGA and EGF in serum and urine depend on a renal permeability.
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PMID:[Serum and urinary cell growth factors in non-insulin-dependent diabetes mellitus]. 223 55

Epidermal and platelet-derived growth factors are potent mitogens for many types of cells, including smooth muscle cells. Epidermal growth factor in blood of humans is present both in platelets (as reflected in its serum level) and in plasma, the source(s) of which remains unknown. We assayed its level in 82 diabetic patients and 53 age-matched controls. In diabetes, epidermal growth factor level was increased in serum (191 +/- 43 vs 155 +/- 64 pmol/l, p = 0.0002) and plasma (53 +/- 9 vs 38 +/- 14 pmol/l, p less than 0.0001), without any difference between the patients with and without complications. Platelet-derived growth factor level was assayed only in serum of 19 patients with uncomplicated diabetes and found elevated (222 +/- 47) as compared with 13 controls (160 +/- 26 pmol/l), (p = 0.0002). Type of diabetes, its duration, mode of therapy, control, presence of retinopathy or albuminuria (in case of epidermal growth factor), as well as C-peptide age and sex did not correlate with epidermal or platelet-derived growth factor levels. Serum but not plasma epidermal and platelet-derived growth factor were negatively correlated with serum creatinine (correspondingly, r = -0.373, p = 0.0008 and r = -0.564, p = 0.0285). It is concluded that diabetes itself and not its complications cause increased levels of epidermal growth factor in plasma and serum and of platelet-derived growth factor in serum.
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PMID:Epidermal growth factor and platelet-derived growth factor in blood in diabetes mellitus. 223 81

Excretion of epidermal growth factor (EGF) is decreased in renal failure. We assayed it in diabetes mellitus in an attempt to relate it to clinical parameters, esp. those of diabetic nephropathy. EGF excretion declined with age but in all age groups of diabetic patients was below the first percentile for controls. In 26 control and 34 prepubertal diabetic children excretion was correspondingly 1126 +/- 442 and 932 +/- 489 pmol/mmol creatinine (P = 0.087); in 26 control and 42 diabetic adolescents below age 18, 778 +/- 222 and 676 +/- 335 (P = 0.023) and in 81 control and 83 diabetic adults, 371 +/- 153 and 235 +/- 140 (P less than 0.0001). Decreased excretion of EGF was seen in some patients without any diabetic complications. Excretion of EGF was independently and inversely correlated with age and duration of diabetes but not with type of diabetes, treatment, body built, C-peptide, plasma glucose, glycohemoglobin or retinopathy. A positive correlation was seen with creatinine clearance and a negative correlation, with albuminuria, but the strongest and the only independent correlation found by stepwise multiple variable selection was with serum creatinine (r -0.711, P less than 0.0001). EGF excretion was not elevated in patients with hyperfiltration. We conclude that EGF excretion is abnormal in many patients with diabetes and that this abnormality reflects a kidney function different from glomerular filtration or glomerular permeability.
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PMID:Excretion of epidermal growth factor (EGF) in diabetes. 228 16

Levels of epidermal growth factor (EGF) in serum were significantly decreased in streptozotocin (STZ)-diabetic mice (446 +/- 168 pg/ml after 1 week and 423 +/- 52 after 4 weeks vs 766 +/- 162 pg/ml in controls, P.002 and less than .001. respectively) and in genetically diabetic ob/ob mice (455 +/- 285 vs 962 +/- 453 pg/ml in nondiabetic ob/+ controls, P.043). The urinary excretion of EGF was significantly increased in STZ mice (104 +/- 53 vs 51 +/- 23 ng/h, P.013) but unchanged in ob/ob mice (33 +/- 9 vs 45 +/- 16 ng/h, P.134). However, when expressed per mg creatinine it was decreased in both cases: in STZ mice to 680 +/- 250 ng/mg at 1 week and 684 +/- 211 at 4 weeks vs 1250 +/- 303 ng/mg in controls (P less than .01); and in the ob/ob mice to 552 +/- 117 vs 1237 +/- 300 ng/mg in ob/+ controls (P less than .01). EGF content of the submandibular glands of STZ mice remained unchanged at 1 week (13.1 +/- 2.9 vs 11.0 +/- 1.8 micrograms/mg protein, P.170) but dropped by 4 weeks (4.7 +/- 1.2 micrograms/mg, P less than .001); in the ob/ob mice it was less than 20% that of controls (2.1 +/- 0.8 vs 12.2 +/- 3.6 micrograms/mg protein). In kidneys, the EGF content was not altered in either ob/ob (524 +/- 50 vs 571 +/- 33 pg/mg protein) or STZ mice (652 +/- 183 vs 665 +/- 80 pg/mg). The preproEGF mRNA level in STZ-treated mice was reduced after 4 weeks in submandibular glands but not in kidneys. The results show that diabetes affects EGF production, utilization and/or excretion in mice and that kidneys are spared from suppression of EGF synthesis that is pronounced in the submandibular glands.
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PMID:Epidermal growth factor in serum, urine, submandibular glands and kidneys of diabetic mice. 240 91

Insulin is a potent mitogen for many cell types in vitro. During tissue culture, supraphysiological concentrations of insulin are necessary to promote cell replication in connective or musculoskeletal tissues. Insulin promotes the growth of these cells by binding, with low affinity, to the type I insulin-like growth factor (IGF) receptor, not through the high affinity insulin receptor. In other cell types, such as hepatocytes, embryonal carcinoma cells, or mammary tumor cells, the type I IGF receptor is virtually absent, and insulin stimulates the growth of these cells at physiological concentrations by binding to the high affinity insulin receptor. Both receptor systems activate phosphorylation reactions within the cell which extend to ribosomal proteins. Insulin acts synergistically with other factors, such as platelet-derived growth factor and epidermal growth factor, to stimulate the progression of cells through the cycle of proliferation. Abnormal insulin secretion or action, before or after birth, often is associated with disordered growth suggesting that insulin may function as a growth factor in vivo. Poor growth follows impaired insulin secretion in diabetes mellitus. This is associated with reduced circulating levels of IGF's which may be partly responsible for the growth failure. Insulin has a direct action on release of IGF's from the liver in vitro, but during experimental diabetes there is a reduced number of hepatic somatotropic receptors which could limit the ability of growth hormone to regulate IGF release. Diabetic children, treated conventionally, have normal circulating IGF levels, but both growth rate and serum IGF concentration may increase dramatically when diabetic control is optimized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin as a growth factor. 241 20

We describe a new familial syndrome in three siblings; it is biochemically characterized by a combined defect of the action of the three related peptides insulin, insulin-like growth factor I (IGF I) and epidermal growth factor (EGF). Clinically, the disease has features of Werner syndrome with lipodystrophy, scleroderma-like alterations of the skin, alterations of the skeleton and contractures of joints. In addition, one of the patients has an insulin-resistant diabetes mellitus. Studies with cultured fibroblasts obtained from skin biopsies show a markedly reduced stimulation of RNA synthesis by the three growth factors and a decreased insulin stimulation of 2-deoxy-D-glucose uptake as compared with normal controls. Receptor binding of the three peptides occurred with normal capacity and affinity. We conclude that the signal transfer of different growth factors has a common denominator at the postreceptor level.
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PMID:A new familial syndrome with impaired function of three related peptide growth factors. 247 23

The production of epidermal growth factor (EGF) in the submandibular gland and its circulating level were studied in diabetic mice. In genetically diabetic (C57BL/KsJ db/db) mice, EGF concentrations in the submandibular gland and plasma were reduced to 13% and 30% of the control levels, respectively. In streptozotocin-treated diabetic mice, they were reduced to 18% and 20% of controls, respectively, 5 weeks after the drug injection. Furthermore, levels of submandibular prepro-EGF mRNA in these diabetic mice were decreased almost in parallel with the glandular EGF concentrations, while there was no change in the levels of submandibular beta-actin mRNA and kidney prepro-EGF mRNA. In addition, histological examination of the submandibular glands indicated that the size of the granular convoluted tubules, which produce EGF, was substantially reduced in the diabetic mice. Insulin administration to streptozotocin-treated mice almost completely reversed the decrease in EGF content in the submandibular gland, substantially elevated the level of the glandular prepro-EGF mRNA and plasma EGF concentration, and increased the size of the granular convoluted tubules in the gland. These results indicate that EGF deficiency occurs in diabetes mellitus and that insulin may be important in maintaining the normal level of EGF in the submandibular gland and plasma.
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PMID:Epidermal growth factor deficiency associated with diabetes mellitus. 247 46

We experimented with a wide range of serum-free media to find the best one for culturing insulinoma cells from the Syrian golden hamster, cell line In-R1-I10. Optimum cell growth came with a mixture of equal proportions of Dulbecco's modified Eagle's medium and Ham's F-12, supplemented with 10(-6) M insulin, 10 micrograms/ml transferrin, and 10(-9) M triiodothyronine (what we labeled DF-ITT medium). In addition to testing different varieties of basal media, we also experimented with different concentrations of known stimulants of cell proliferation, including transferrin, ferrous sulfate, insulin, epidermal growth factor, triiodothyronine, hydrocortisone, monoethanolamine, prolactin, proteose peptone, and selenium. Cells cultured in DF-ITT medium grew as well as those in serum-containing medium for 94 consecutive generations. Their insulin secreting capacity was maintained. The substitution of epidermal growth factor (10 ng/ml) for the insulin did not reduce either the growth rate or the insulin secreting capacity of the culture cells.
Diabetes Res Clin Pract 1989 Jan 03
PMID:Serum-free culture of insulin-secreting clonal cells from a hamster insulinoma. 253 87

Urinary epidermal growth factor (EGF) excretion was calculated as ng EGF per mg creatinine and ng EGF per 24 hr. It was increased 4-9 fold in rats with genetic (BB) or streptozotocin-induced diabetes. It decreased to 2-3 fold control values in insulin-treated animals. In contrast, EGF concentration in serum was lower in diabetic than in control rats (360 +/- 72 vs 524 +/- 150 pg/ml, P .086); EGF level in plasma was unchanged (319 +/- 67 vs 313 +/- 96 pg/ml). In diabetic rats EGF content was increased in submaxillary glands (1018 +/- 259 vs 738 +/- 122 pg/mg protein, P .060) but unchanged in the kidneys (70 +/- 18 vs 65 +/- 6 pg/mg protein in controls). EGF binding to the liver microsomes in diabetic rats was decreased by 30-40% and was not restored by insulin therapy. Binding to the kidneys also showed a tendency to decrease in diabetic animals. The EGF excretion and receptor binding were normal in obese normoglycemic Zucker fa/fa rats. We suggest that hyperglycemia and/or glucosuria may affect EGF synthesis and/or excretion in the kidneys and EGF synthesis or accumulation in the megakaryocytes. The mechanism of decreased EGF receptor binding remains to be clarified.
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PMID:Epidermal growth factor excretion and receptor binding in diabetic rats. 264 98


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