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Allan Flyvbjerg

Publications and source records attributed to Allan Flyvbjerg.

At least 73 records · Page 4Linked to original sources
PubMed2004

Transforming growth factor beta1-induced glomerulopathy is prevented by 17beta-estradiol supplementation.

Transforming growth factor beta1 (TGF-beta1) affects extracellular matrix (ECM) accumulation. It plays a role in the thickening of the peripheral basement membrane (PBM) and expansion of the mesangium in several renal diseases. The beneficial influence of female gender on the progression of chronic renal diseases may be explained by a favorable effect of estrogen on ECM homeostasis. Interactions between TGF-beta1 and estrogen have been investigated in mesangial cell cultures. However, it is unknown if TGF-beta1-induced glomerulopathy in vivo is influenced by exogenous estrogen. Thus, the aim of the present experiment was to explore whether estrogen prevents the development of TGF-beta1-induced glomerular disease in transgenic mice expressing active TGF-beta1 under control of the Ren-1c promoter. Mice were treated from 3 weeks to 6 weeks of age with 17beta-estradiol release pellets (5-10 microg/kg body weight per day). At the age of 6 weeks, all investigated animals were sacrificed for estimation of PBM thickness, the mesangium per glomerulus [Vv(mes/glom)], the mesangial matrix per glomerulus [Vv(matrix/glom)] and the PBM per glomerulus [Vv(PBM/glom)] using electron microscopy and stereological methods. Furthermore, the total collagen content was determined. We found that TGF-beta1-induced alterations in Vv(mes/glom), Vv(matrix/glom) and Vv(PBM/glom) were prevented in mice exposed to exogenous 17beta-estradiol. In addition, the interstitial fibrosis that develops in TGF-beta1 transgenic mice was attenuated by administration of 17beta-estradiol. In conclusion, estrogen may oppress TGF-beta1-mediated kidney diseases and, thereby, contribute to the protracted development of end-stage renal disease in pre-menopausal women.

Animals↗
PubMed2004

Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes.

BACKGROUND: Type 2 diabetes has become the single most frequent cause of end-stage renal disease. The Goto-Kakizaki rat is currently used as a model for lean type 2 diabetes, but its renal changes have not been fully characterized. We investigated long-term functional and structural renal changes in the Goto-Kakizaki rat to evaluate if this animal model resembles the changes observed in human diabetic kidney disease. METHODS: Urinary albumin excretion, creatinine clearance and blood pressure were measured at the age of 2, 8 and 14 months in 12 female Goto-Kakizaki rats and 10 female, non-diabetic Wistar rats. To study kidney morphology, kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were determined at 14 months. RESULTS: Urinary albumin excretion rose progressively over time in both groups, but was significantly higher in Goto-Kakizaki rats than in Wistar rats. Creatinine clearance decreased over time in Goto-Kakizaki rats but not in Wistar rats. Blood pressure was in the normotensive range in all animals throughout the study. Kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were significantly higher in Goto-Kakizaki rats than in Wistar rats. Body weight and blood glucose levels were higher, whereas serum insulin levels were not different or lower in Goto-Kakizaki rats compared with Wistar rats. CONCLUSION: The Goto-Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.

Albuminuria↗
PubMed2004

Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats.

Patients with growth hormone deficiency (GHD) have an increased risk of bone fractures. In these patients, the well-described decrease in bone mineral density (BMD) and content (BMC) may, however, not alone explain the increase in fracture rate. Accordingly, the aim of this study was to evaluate collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10% and growth rate to approximately 40-50% when compared to normal control rats. Five male Dw-4 rats were examined at age 12 weeks and five healthy Lewis rats served as age-matched controls. The animals were examined for (1) bone mineral status by dual energy X-ray absorptometry (DXA) and ash weight/bone volume, (2) biomechanical properties, (3) serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and (4) collagen morphology of cortical bone from the right femurs was examined by scanning and transmission electron microscopy. A significant decrease was found in serum IGF-I, IGFBP-3 and biomechanical properties in GHD rats compared to controls (P < 0.009). While DXA-derived BMD was decreased, no significant difference was found in ash weight/bone volume. Electron microscopy showed a significant decrease in the number and a significant increase in the diameter of collagen microfibrils in GHD rats as compared to their controls (P < 0.009). In conclusion, we report for the first time that collagen morphology in bone is markedly altered in rats with isolated GHD. Whether similar conditions are present in GHD patients need further investigations. The changes described, however, may provide a co-explanation for the increased fracture rate in GHD.

Absorptiometry, Photon↗
PubMed2004

High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.

OBJECTIVE: To assess the effect of pegvisomant-induced serum insulin-like growth factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2 and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly. DESIGN: The above parameters were measured in 16 patients (median age 57 (range 27-78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range after washout) in a paired manner on samples obtained after washout and the first occurrence of serum IGF-I normalization during pegvisomant therapy (median dose 15 mg/day (10-40 mg)). RESULTS: Total IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly elevated in patients at baseline compared to controls ((mean+/-SEM) 4345+/-194 vs. 3456+/-159 microg/L, P<0.01 and 3908+/-160 va. 3042+/-149 microg/L, P<0.01, respectively), but no significant difference in 45-kDa IGFBP-3 or in vivo IGFBP-3 proteolysis was observed. Serum IGF-I normalization (699+/-76 to 242+/-28 microg/L, P<0.0001) was associated with a fall in total IGFBP-3 (4345+/-194 to 3283+/-160 microg/L, P<0.001) due to a reduction in 150-kDa ternary complex-associated IGFBP-3 (3908+/-160 to 3008+/-140 microg/L, P<0.0001). 45 kDa IGFBP-3 and in vivo IGFBP-3 proteolysis were unaffected by GH receptor blockade (326+/-13 to 330+/-18 microg/L, P=0.86; 30+/-3.5 to 30+/-3.9%, P=0.75, respectively). CONCLUSIONS: GH receptor blockade in patients with acromegaly lowers IGF-I and 150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary complex-associated IGFBP-3 may provide useful information regarding treatment efficacy in patients with acromegaly.

Acromegaly↗
PubMed2004

The physiological and pathophysiological roles of the GH/IGF-axis in the kidney: lessons from experimental rodent models.

The growth hormone (GH)/insulin-like growth factor (IGF) system plays an important role in renal development, growth, function and pathophysiology. IGF-I has been associated with renal/glomerular hypertrophy and compensatory renal growth. Potential effects on glomerular size are of interest, since an increase in glomerular size may be permissive for the development of glomerulosclerosis. In an effort to abolish the decline of renal function and possibly to restore the renal structure, different approaches have been tested in experimental models of nephropathy, focusing mainly on early renal changes. The involvement of the GH/IGF system in renal pathophysiology has been studied in much detail in the rat. In view of the growing interest in murine physiology, occurring in large part by genetically modified animals, this review examines those aspects of GH, IGFs, their receptors and binding proteins that relate both to mouse kidney physiology and to a number of conditions characterized by pathophysiological renal changes. A deeper understanding of the role of the GH/IGF system in renal dysfunction may stimulate the development of novel therapeutic approaches aiming at preventing or retarding various kidney diseases.

Animals↗
PubMed2004

Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients.

Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV-lipodystrophy. These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin concentration were increased (>90%, P < .01) and insulin sensitivity (Log10ISI(composite)) was decreased (-50%, P < .001). Total and free IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease were similar between groups (all P > .5), whereas, in LIPO, IGFBP-1 and IGFBP-2 were reduced (-36%, P < .05 and -50%, P < .01). In pooled groups, total IGF-I, free IGF-I, total IGF-II, and IGFBP-3, respectively, correlated inversely with age (all P < .01). In pooled groups, IGFBP-1 and IGFBP-2 correlated positively with insulin sensitivity (age-adjusted all P < .05). IGFBP-3 protease correlated with free IGF-I in pooled groups (r(p) = 0.47, P < .02), and in LIPO (r(p) = 0.71, P < .007) controlling for age, total IGF-I, and IGFBP-3. GHBP was increased, whereas GH was decreased in LIPO (all P < .05). GH correlated inversely with GHBP in pooled groups (P < .05). Taken together the similar IGFs and IGFBP-3 concentrations between study groups, including suppressed GH, and increased GHBP in LIPO, argue against GH resistance of GH-sensitive tissues in LIPO compared with NONLIPO; however, this notion awaits examination in dose-response studies. Furthermore, our data suggest that IGFBP-3 protease is a significant regulator of bioactive IGF-I in HIV-lipodystrophy.

Age Factors↗
PubMed2004

Different growth hormone sensitivity of target tissues and growth hormone response to glucose in HIV-infected patients with and without lipodystrophy.

Growth hormone (GH)-secretion in HIV-lipodystrophy is impaired; however, GH-sensitivity of GH-target tissues remains to be evaluated. We measured overnight fasting concentrations of GH-sensitive insulin-like growth-factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) including GH binding protein (GHBP), a marker of GH-receptor sensitivity, in antiretroviral treated HIV-infected patients with (LIPO) and without lipodystrophy (NONLIPO) and antiretroviral naive HIV-infected patients (NAIVE). Three h GH-suppression tests using oral glucose were undertaken to determine dynamics of GH-secretion. IGF-I and IGFBP-3 were increased in LIPO compared with NONLIPO (p <0.05), but did not differ significantly between NONLIPO and NAIVE. Area under the curve of GH (AUC-GH) during the GH-suppression test was decreased in LIPO compared with NONLIPO (p <0.05). Ratio of limb to trunk fat, which was decreased in LIPO compared to NONLIPO and NAIVE (p <0.001), correlated positively with AUC-GH and rebound-GH (p <0.05). All groups displayed suppression of GH during the suppression test (p <0.05) and all groups, except LIPO, displayed a rebound of GH (p <0.05), which probably is explained by persistently increased plasma glucose in LIPO compared with NONLIPO and NAIVE (p <0.01). GHBP was inversely correlated with AUC-GH (p <0.01). Our data suggest that GH-target tissues in LIPO are at least as GH-sensitive as in HIV-infected patients without lipodystrophy.

Absorptiometry, Photon↗
PubMed2004

The role of vascular endothelial growth factor (VEGF) in renal pathophysiology.

Vascular endothelial growth factor (VEGF) is an endothelial-specific growth factor that promotes endothelial cell proliferation, differentiation and survival, mediates endothelium-dependent vasodilatation, induces microvascular hyperpermeability and participates in interstitial matrix remodeling. In the kidney, VEGF expression is most prominent in glomerular podocytes and in tubular epithelial cells, while VEGF receptors are mainly found on preglomerular, glomerular, and peritubular endothelial cells. The role of VEGF in normal renal physiology is essentially unknown. The absence of prominent effects of VEGF blockade in normal experimental animals suggests a limited function during homeostasis, although a role in the formation and maintenance of glomerular capillary endothelial fenestrations has been suggested. VEGF and its receptors are up-regulated in experimental animals and humans with type 1 and type 2 diabetes. Inhibition of VEGF has beneficial effects on diabetes-induced functional and structural alterations, suggesting a deleterious role for VEGF in the pathophysiology of diabetic nephropathy. VEGF is required for glomerular and tubular hypertrophy and proliferation in response to nephron reduction, and loss of VEGF is associated with the development of glomerulosclerosis and tubulointerstitial fibrosis in the remnant kidney. No firm conclusions on the role of VEGF in minimal change or membranous glomerulonephritis can be drawn. VEGF may be an essential mediator of glomerular recovery in proliferative glomerulonephritis. Glomerular and tubulointerstitial repair in thrombotic microangiopathy and cyclosporin nephrotoxicity may also be VEGF-dependent. In conclusion, VEGF is required for growth and proliferation of glomerular and peritubular endothelial cells. While deleterious in some, it may contribute to recovery in other forms of renal diseases.

Animals↗
PubMed2004

From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines.

At present, diabetic kidney disease affects about 15-25% of type 1 and 30-40% of type 2 diabetic patients. Several decades of extensive research has elucidated various pathways to be implicated in the development of diabetic kidney disease. This review focuses on the metabolic factors beyond blood glucose that are involved in the pathogenesis of diabetic kidney disease, i.e., advanced glycation end-products and the aldose reductase system. Furthermore, the contribution of hemodynamic factors, the renin-angiotensin system, the endothelin system, and the nitric oxide system, as well as the prominent role of the intracellular signaling molecule protein kinase C are discussed. Finally, the respective roles of TGF-beta, GH and IGFs, vascular endothelial growth factor, and platelet-derived growth factor are covered. The complex interplay between these different pathways will be highlighted. A brief introduction to each system and description of its expression in the normal kidney is followed by in vitro, experimental, and clinical evidence addressing the role of the system in diabetic kidney disease. Finally, well-known and potential therapeutic strategies targeting each system are discussed, ending with an overall conclusion.

Aldehyde Reductase↗
PubMed2004

Residual beta-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes.

The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual beta-cell function. Patients with hemoglobin A1c (HbA1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 +/- 13.8 yr (mean +/- SD), with a diabetes duration of 17.8 +/- 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 +/- 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA1c was 5.6 +/- 0.5% in patients and 4.4 +/- 0.3% in controls. Total IGF-I was 148 +/- 7 microg/liter in patients and 178 +/- 9 microg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (> or =100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual beta-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

Adult↗
PubMed2004

Serum adiponectin levels in adults with Prader-Willi syndrome are independent of anthropometrical parameters and do not change with GH treatment.

OBJECTIVE: Obesity and growth hormone (GH) deficiency are common in Prader-Willi syndrome (PWS) and these patients are at risk of metabolic diseases in adult life and of reduced life span. Low adiponectin values are associated with obesity and the metabolic syndrome. We therefore found it of interest to measure adiponectin levels in PWS. PATIENTS AND METHODS: 17 adults, nine men and eight women, 17 to 32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2 participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin) for six months, and subsequently all received GH for 12 months. At baseline, serum total adiponectin levels in the PWS patients were compared with 25 lean and 34 obese controls. Body composition and various metabolic parameters, including adiponectin, were studied every six months in the PWS group. RESULTS: Serum adiponectin levels in PWS subjects were significantly lower (P<0.001) compared with lean and significantly higher (P<0.001) compared with obese controls. In PWS patients, no correlation was found between adiponectin and anthropometrical parameters or measures of insulin sensitivity (e.g. fasting insulin and insulin sensitivity as estimated by the homeostasis model assessment), or between adiponectin and IGF binding protein-1 or IGF-I. Adiponectin did not change during GH intervention. CONCLUSION: In this study of adults with PWS serum total adiponectin levels were higher than in controls with simple obesity and were independent of anthropometrical parameters. In accordance with this the metabolic syndrome is not necessarily present in all PWS patients. Correction of GH deficiency had no effect on serum adiponectin levels.

Adiponectin↗
PubMed2004

The involvement of growth hormone (GH), insulin-like growth factors (IGFs) and vascular endothelial growth factor (VEGF) in diabetic kidney disease.

At present, diabetic kidney disease affects about 15-25 % of patients with type 1 diabetes (T1D) and 30-40 % of patients with type 2 diabetes (T2D). Several decades of extensive research have elucidated various pathways to be implicated in the development of diabetic kidney disease. These include metabolic factors beyond blood glucose (e.g. advanced glycation endproducts (AGEs)), haemodynamic factors (e.g. the renin angiotensin system (RAS)), intracellular signaling molecule proteins (e.g. protein kinase C (PKC)) and growth factors/cytokines (e.g. growth hormone (GH), insulin-like growth factors (IGFs), transforming growth factor beta (TGF-beta) and vascular endothelial growth factor (VEGF)). This review focuses on the role of three of these growth factors, i.e. GH, IGFs and VEGF. A brief discussion of each system is followed by description of its expression in the normal kidney. Then, for each system, in vitro, experimental and clinical evidence addressing the role of the system in diabetic kidney disease is presented. The interplay of each system to other potential pathways will also be addressed. Finally, well-known and potential therapeutic strategies targeting the GH/IGF and VEGF systems in a specific or indirect way will discussed.

Animals↗
PubMed2004

Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice.

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor-mediated pathway and through specific receptors for AGE (RAGEs). To explore a specific role for RAGE in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine RAGE antibody in db/db mice, a model of obese type 2 diabetes. One group of db/db mice was treated for 2 months with the RAGE antibody, and another db/db group was treated for the same period with an irrelevant IgG. Two groups of nondiabetic db/+ mice were treated with either RAGE antibody or isotype-matched IgG for 2 months. Placebo-treated db/db mice showed a pronounced increase in kidney weight, glomerular volume, basement membrane thickness (BMT), total mesangial volume, urinary albumin excretion (UAE), and creatinine clearance compared with nondiabetic controls. In RAGE antibody-treated db/db mice, the increase in kidney weight, glomerular volume, mesangial volume, and UAE was reduced, whereas the increase in creatinine clearance and BMT was fully normalized. Notably, these effects in db/db mice were seen without impact on body weight, blood glucose, insulin levels, or food consumption. In conclusion, RAGE is an important pathogenetic factor in the renal changes in an animal model of type 2 diabetes.

Albuminuria↗
PubMed2004

Association between mannose-binding lectin and vascular complications in type 1 diabetes.

Complement activation and inflammation have been suggested in the pathogenesis of diabetic vascular lesions. We investigated serum mannose-binding lectin (MBL) levels and polymorphisms in the MBL gene in type 1 diabetic patients with and without diabetic nephropathy and associated macrovascular complications. Polymorphisms in the MBL gene and serum MBL levels were determined in 199 type 1 diabetic patients with overt nephropathy and 192 type 1 diabetic patients with persistent normoalbuminuria matched for age, sex, and duration of diabetes, as well as in 100 healthy control subjects. The frequencies of high- and low-expression MBL genotypes were similar in patients with type 1 diabetic and healthy control subjects. High MBL genotypes were significantly more frequent in diabetic patients with nephropathy than in the normoalbuminuric group, and the risk of having nephropathy given a high MBL genotype assessed by odds ratio (OR) was 1.52 (1.02-2.27, P = 0.04). Median serum MBL concentrations were significantly higher in patients with nephropathy than in patients with normoalbuminuria: 2,306 microg/l (interquartile range [IQR] 753-4,867 microg/l) vs. 1,491 microg/l (577-2,944 microg/l), P = 0.0003. In addition, even when comparing patients with identical genotypes, serum MBL levels were higher in the nephropathy group than in the normoalbuminuric group. Patients with a history of cardiovascular disease had significantly elevated MBL levels independent of nephropathy status (3,178 microg/l [IQR 636-5,231 microg/l] vs. 1,741 microg/l [656-3,149 microg/l], P = 0.02). The differences in MBL levels between patients with and without vascular complications were driven primarily by pronounced differences among carriers of high MBL genotypes (P < 0.0001). Our findings suggest that MBL may be involved in the pathogenesis of micro- and macrovascular complications in type 1 diabetes, and that determination of MBL status might be used to identify patients at increased risk of developing these complications.

Adult↗
PubMed2004

Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women.

BACKGROUND: Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and IGFBP-3 protease activity and breast cancer risk in postmenopausal women, taking ER status of the breast cancer into consideration. METHODS: We conducted this case-cohort study within a Danish follow-up study based on 24,697 postmenopausal women. We identified 411 cases with breast cancer and a matched control group including 397 cohort members. We estimated breast cancer risk using Cox regression analysis with adjustment for known breast cancer risk factors. RESULTS: We observed no association for IGF-I but a positive association between levels of IGFBP-3 and breast cancer risk. Per 500 units higher levels of IGFBP-3, an incidence rate ratio [IRR; 95% confidence interval (95% CI)] of 1.14 (1.00-1.30) was estimated. For ER-positive breast cancer, the IRR (95% CI) was 1.18 (1.05-1.33). IGFBP-3 protease activity was not associated with breast cancer risk. Per 275 units higher levels of IGF-II, an IRR (95% CI) of 1.35 (1.10-1.66) was observed for ER-positive tumors, whereas IGFBP-2 was not associated with breast cancer risk. Adjustment for potential confounders did not change the risk estimate. There was no association between IGF-I, IGF-II, IGFBP-2, or IGFBP-3 and risk of ER-negative breast cancer. CONCLUSION: Serum IGFBP-3 and IGF-II levels were positively associated with ER-positive breast cancer risk. This may suggest an important relationship among IGFs, IGFBPs, the ER system, and breast cancer development in postmenopausal women.

Breast Neoplasms↗
PubMed2004

The role of growth hormone in the pathogenesis of diabetic kidney disease.

At present, diabetic kidney disease affects about 15-20% of all Type 1 diabetic patients and 20-40% of all patients with Type 2 diabetes. Preclinical research performed over the past decade has suggested growth hormone (GH) and insulin-like growth factors (IGFs) to be involved in the pathogenesis of diabetic kidney disease. Data obtained in knock-out (KO) mice with GH receptor (GHR)/GH binding protein (GHBP) gene-disruption have shown that these animals are protected against diabetes-induced renal changes. Further, diabetic mice treated with either a longacting somatostatin analogue or a specific GHR antagonist (GHRA) showed normalization of the diabetes-associated renal hypertrophy and glomerular enlargement and most importantly also a lowering effect on the diabetes-induced rise in urinary albumin excretion (UAE), a marker of renal damage. Based on these experimental data future studies are warranted to characterize the clinical potential of GH-inhibitors (e.g. GHRAs) as drugs for the treatment of diabetic renal complications.

Animals↗