Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Type 1 diabetes, poor glycemic control is the key predictor for the development of microalbuminuria, an established early marker of overt nephropathy. However, the role of other pathways in the development of diabetic nephropathy may also be important. The growth hormone (GH) hypothesis suggests that the GH-insulin-like growth factor (IGF)-1 axis may play an important role in this disease process. In Type 1 diabetes, the characteristic pattern of GH hypersecretion and low circulating IGF-1 levels results from hepatic GH resistance owing to the lack of portal insulin. Clinical data indicate that high GH and low IGF-1 levels reduce insulin sensitivity and worsen glycemic control. Furthermore, despite hepatic GH resistance, GH receptors at the kidney remain intact. Experimental data show that excess GH stimulates renal GH receptors and, through paracrine IGF-1 production, results in pathophysiological changes consistent with diabetic nephropathy, namely nephromegaly, glomerular hyperfiltration and eventual proteinuria. These abnormalities are reversed by intervention to block or normalize the local effects of GH and IGF-1. Although such data in humans are limited, preliminary trials show that interventions to increase IGF-1 levels and reduce GH hypersecretion improve glycemic control and insulin sensitivity in the short term. However, their effects on early nephropathy and end points, such as the prevalence of end stage renal disease, have yet to be determined.
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PMID:Growth hormone hypothesis and development of diabetic nephropathy in Type 1 diabetes. 3075 96

Despite decades of study on the contribution of growth hormone (GH) to the development of kidney disease, there remains the question of the relative contribution of elevated levels of GH to kidney damage in humans, particularly in diabetic nephropathy occurring in type 1 patients. In this study, we reviewed several publicly available datasets to examine transcription of twelve genes associated with the GH/IGF1 axis in several types of human and rodent kidney diseases. Our analyses revealed downregulation of renal GHR and IGF1 gene expression in several different chronic human kidney diseases, including diabetic nephropathy, with general upregulation of IGFBP6 in the same tissues and diseases. These findings were generally supported by a review of studies in rodent models. In healthy and diseased human kidneys, increased GHR gene expression was associated with increases in glomerular filtration rate (GFR) and decreases in serum creatinine. IGFBP6 gene expression demonstrated the opposite clinical correlation. Our results suggest the kidney may exhibit GH insensitivity due to low GHR gene expression during most chronic kidney diseases.
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PMID:A review of renal GH/IGF1 family gene expression in chronic kidney diseases. 3135 57

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease. We treated a 50-year-old male with diabetes mellitus who showed a sudden and rapid decline of renal function along with increasing proteinuria, which led to diagnoses of PKD and acromegaly. His urinary protein levels were increased together with excessive GH secretion and worsening glycemic control. An increase of total kidney volume was also noted. Transsphenoidal surgery for the pituitary adenoma was successfully performed. Marked improvement of hyperglycemia and proteinuria were observed after the surgery, but renal function was unchanged. The patient's clinical course suggested common aspects of excessive GH secretion as an accelerating factor of the progression of diabetic nephropathy and PKD via direct and indirect pathways. Although coexisting acromegaly and PKD is clinically rare, vigilance for early diagnosis of acromegaly is appropriate in patients with diabetes and/or PKD, especially in those showing unexpected exacerbation of renal dysfunction.
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PMID:Acromegaly accompanied by diabetes mellitus and polycystic kidney disease. 3281 22


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