Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human insulin-like growth factor I (rhIGF-I) lowers blood glucose, serum insulin, C-peptide, and lipid levels in healthy and diabetic animals and humans. We hypothesized that rhIGF-I might control blood glucose levels and concomitantly reduce pancreatic insulin secretion in patients with type II diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate some of the detrimental effects of hyperinsulinemia secondary to insulin resistance in these patients. In this study, we treated 12 patients with type II diabetes mellitus twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or 160 micrograms/kg body weight. Metabolic parameters in the fasting and postprandial states were assessed during a 3-day baseline period, the rhIGF-I treatment period, and a 3-day follow-up period, respectively. Administration of rhIGF-I significantly reduced mean (+/- SD) concentrations of fasting blood glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum insulin (98 +/- 52 to 56 +/- 27 pmol/L), and C-peptide (993 +/- 298 to 728 +/- 232 pmol/L). It also decreased postprandial (area under the curve) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1 mmol/L.h), serum insulin (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide (5958 +/- 2747 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also associated with a small but significant reduction in serum triglycerides (6.76 +/- 3.45 to 5.32 +/- 2.59 mmol/L) and total cholesterol (6.13 +/- 1.25 to 5.66 +/- 1.20 mmol/L), 24-h creatinine clearance increased significantly (85 +/- 30 to 133 +/- 51 mL/min), and microalbuminuria was unchanged. Although rhIGF-I was reasonably well tolerated, side effects included low-grade edema, mild and mainly asymptomatic orthostatic hypotension, and bilateral temporomandibular tenderness. We conclude that short-term treatment of type II diabetic patients with rhIGF-I favorably affects metabolic control and enhances kidney function. An assessment of the risk/benefit ratio of rhIGF-I administration to this group of patients awaits extended experiments.
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PMID:Short-term effects of recombinant human insulin-like growth factor I on metabolic control of patients with type II diabetes mellitus. 826 42

Glomerular hyperfiltration is a characteristic feature of acromegaly but it is uncertain whether albuminuria is elevated in this disease. To investigate the role of abnormal growth hormone (GH) and insulin-like growth factor I (IGF-I) levels on urinary protein excretion, we measured the overnight urinary albumin excretion rate (UalbV) and creatinine clearance in 14 acromegalic patients with metabolically active disease (fasting GH > 5 micrograms/l and IGF-I > 2.2 kU/l), 8 GH-deficient patients and 20 control subjects. The UalbV was higher in the acromegalic patients (median 8.4 (range 4.2-68.2) micrograms/min) than in the GH-deficient patients (2.0 (0.9-5.9) micrograms/min, p < 0.001) and control subjects (3.3 (1.0-7.8) micrograms/min, p < 0.01). Five acromegalic patients had UalbV levels above the normal upper normal limit of 10 micrograms/min. Only one patient with concomitant untreated hypertension had persistent microalbuminuria. Creatinine clearance also was higher in the acromegalic patients (p < 0.05) and lower in the GH-deficient patients (p < 0.05) than in the control subjects. In 11 of these acromegalic cases, the lowering of GH by 63% and of IGF-I by 48%, following treatment with the somatostatin analogue (N = 10) or spontaneous pituitary infarction (N = 1), reduced the UalbV by 29% to 4.9 (3.1-45.2) micrograms/min (p < 0.01). Among the acromegalic patients (25 observations), the UalbV was related to GH (r = 0.61, p < 0.01), IGF-I (r = 0.57, p < 0.01) and creatinine clearance (r = 0.54, p < 0.01). In conclusion, circulatory GH and IGF-I levels influence albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of growth hormone and insulin-like growth factor I on urinary albumin excretion: studies in acromegaly and growth hormone deficiency. 837

This article reviews data that have accumulated since the early 1970s on the role of the dorsomedial hypothalamic nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial hypothalamic nucleus (VMN) and the lateral hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.
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PMID:The dorsomedial hypothalamic nucleus revisited: 1998 update. 971 72

Microalbuminuria is the earliest detectable clinical abnormality in diabetic glomerulopathy. On a molecular level, metabolic pathways activated by hyperglycemia, glycated proteins, hemodynamic factors, and oxidative stress are key players in the genesis of diabetic kidney disease. A variety of growth factors and cytokines are then induced through complex signal transduction pathways. Transforming growth factor-beta 1 (TGF-beta1) has emerged as an important downstream mediator for the development of renal hypertrophy and the accumulation of mesangial extracellular matrix components, but there is limited evidence to support its role in the development of albuminuria. The loss of proteoglycans in the glomerular basement membrane (GBM) has been recently questioned as causative of the albuminuria, and current research has focused on the podocyte as a central target for the effects of the metabolic milieu in the development and progression of diabetic albuminuria. Podocyte-derived vascular endothelial growth factor (VEGF), a permeability and angiogenic factor whose expression is increased in diabetic kidney disease, is perhaps a major mediator of the increased protein filtration. Decreased podocyte number and/or density as a result of apoptosis or detachment, GBM thickening with altered matrix composition, and a reduction in nephrin protein in the slit diaphragm with podocyte foot process effacement, all comprise the principal features of diabetic podocytopathy that clinically manifests as albuminuria and proteinuria. Many of these events are mediated by angiotensin II whose local concentration is stimulated by high glucose, mechanical stretch, and proteinuria itself. Angiotensin II in turn stimulates podocyte-derived VEGF, suppresses nephrin expression, and induces TGF-beta1 leading to podocyte apoptosis and fostering the development of glomerulosclerosis. Proteinuria can then induce in tubular cells a genetic program leading to tubulointerstitial inflammation, fibrosis and tubular atrophy. Besides direct effects of albuminuria on tubular cells, pathophysiological changes in the ultrafiltration barrier lead to an increased tubular filtration of various growth factors (TGF-beta1, insulin-like growth factor I) that may further alter the function of tubular cells. Moreover, angiotensin II also stimulates uptake of ultrafiltered proteins into tubular cells and enhances the production of proinflammatory and profibrotic cytokines within the cells. Migration of macrophages and other inflammatory cells into the tubulointerstitium occurs. Increased synthesis and decreased turnover of extracellular matrix proteins in tubular cells and interstitial fibroblasts contribute to interstitial fibrosis. In addition, under locally high concentrations of angiotensin II and TGF-beta1, tubular cells may change their phenotype and become fibroblasts by a process called epithelial to mesenchymal transition (EMT) which contributes to interstitial fibrosis and tubular atrophy because of vanishing epithelia cells. An alternative explanation for the development of albuminuria in diabetic nephropathy that involves primarily an abnormality in tubular handling of ultrafiltered proteins has also been suggested, but these changes are not necessarily exclusive of the altered properties of glomerular ultrafiltration barrier.
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PMID:Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. 1822 Jun 94