A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our ...A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.展开更多
Objective:To observe the change of fibroblast growth factor-2(FGF-2),insulin-like growth factor-1(IGF—1)in serum and bone callus after fracture in diabetic rats,and to explore molecular biological mechanism of healin...Objective:To observe the change of fibroblast growth factor-2(FGF-2),insulin-like growth factor-1(IGF—1)in serum and bone callus after fracture in diabetic rats,and to explore molecular biological mechanism of healing of diabetic fracture.Methods:Thirty male SD rats were designed into normal(n=13)and control(n=!5)groups randomly.Venous blood was extracted on the 1st,2nd,4th,6th,8th week after surgery.It was certificated and the serum was obtained.Left lower extremity was observed by X-ray.Bone callus at broken ends was observed under light microscope.Expressions of FGF-2 and 1GF-1 in tissue were detected by immunohistochemistry method,and ELISA was used to detect expression of FGF-2 and IGF-I in serum.Results:The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of normal rats compared to control rats.Increased cell proliferation was also found in the distraction gaps of normal rats versus control rats.There was significant difference in serum levels of FGF-2 and IGF-1 between two groups.Conclusions:The decrease of FGF-2 and IGF-1 both in the serum and in the fracture region is one of the reasons for bad bone healing or delayed union in rats'fracture with diabetes.There are some synergistic effects possibly between FGF-2 and ICF-I.展开更多
Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but ...Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 （CCN4） to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.展开更多
Incretins are gut-produced peptide-hormones that potentiate insulin secretion,especially after food intake.The concept of incretin was formed more than 100 years ago,even before insulin was isolated and utilized in th...Incretins are gut-produced peptide-hormones that potentiate insulin secretion,especially after food intake.The concept of incretin was formed more than 100 years ago,even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes.The first incretin,glucose-dependent insulinotropic polypeptide(GIP),was identified during later 1960’s and early 1970’s;while the second one,known as glucagon-like peptide-1(GLP-1),was recognized during 1980’s.Today,GLP-1-based therapeutic agents[also known as GLP-1 receptor(GLP-1R)agonists,GLP-1RAs]are among the first line drugs for type 2 diabetes.In addition to serving as incretin,extra-pancreatic functions of GLP-1RAs have been broadly recognized,including those in the liver,despite the absence of GLP-1R in hepatic tissue.The existence of insulin-independent or gut-pancreas-liver axis-independent hepatic function of GLP-1RAs explains why those therapeutic agents are effective in subjects with insulin resistance and their profound effect on lipid homeostasis.Following a brief review on the discovery of GLP-1,we reviewed literature on the exploration of hepatic function of GLP-1 and GLP-1RAs and discussed recent studies on the role of hepatic hormone fibroblast growth factor 21(FGF21)in mediating function of GLP-1RAs in animal models.This was followed by presenting our perspective views.展开更多
基金supported by the National Natural Science Foundation of China (No.81070687 and 8117-0805)National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(Grant No.2008ZX09312-016)Beijing Natural Science Foundation(No.7121012)
文摘A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.
基金supported by Fujian Medical Innovation Subject Project(2012-CX-29)
文摘Objective:To observe the change of fibroblast growth factor-2(FGF-2),insulin-like growth factor-1(IGF—1)in serum and bone callus after fracture in diabetic rats,and to explore molecular biological mechanism of healing of diabetic fracture.Methods:Thirty male SD rats were designed into normal(n=13)and control(n=!5)groups randomly.Venous blood was extracted on the 1st,2nd,4th,6th,8th week after surgery.It was certificated and the serum was obtained.Left lower extremity was observed by X-ray.Bone callus at broken ends was observed under light microscope.Expressions of FGF-2 and 1GF-1 in tissue were detected by immunohistochemistry method,and ELISA was used to detect expression of FGF-2 and IGF-I in serum.Results:The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of normal rats compared to control rats.Increased cell proliferation was also found in the distraction gaps of normal rats versus control rats.There was significant difference in serum levels of FGF-2 and IGF-1 between two groups.Conclusions:The decrease of FGF-2 and IGF-1 both in the serum and in the fracture region is one of the reasons for bad bone healing or delayed union in rats'fracture with diabetes.There are some synergistic effects possibly between FGF-2 and ICF-I.
基金supported by the following grants to KM:American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 （CCN4） to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.
基金supported by the Canadian Institute of Health Research (PJT159735 to T.J.).
文摘Incretins are gut-produced peptide-hormones that potentiate insulin secretion,especially after food intake.The concept of incretin was formed more than 100 years ago,even before insulin was isolated and utilized in the treatment of subjects with type 1 diabetes.The first incretin,glucose-dependent insulinotropic polypeptide(GIP),was identified during later 1960’s and early 1970’s;while the second one,known as glucagon-like peptide-1(GLP-1),was recognized during 1980’s.Today,GLP-1-based therapeutic agents[also known as GLP-1 receptor(GLP-1R)agonists,GLP-1RAs]are among the first line drugs for type 2 diabetes.In addition to serving as incretin,extra-pancreatic functions of GLP-1RAs have been broadly recognized,including those in the liver,despite the absence of GLP-1R in hepatic tissue.The existence of insulin-independent or gut-pancreas-liver axis-independent hepatic function of GLP-1RAs explains why those therapeutic agents are effective in subjects with insulin resistance and their profound effect on lipid homeostasis.Following a brief review on the discovery of GLP-1,we reviewed literature on the exploration of hepatic function of GLP-1 and GLP-1RAs and discussed recent studies on the role of hepatic hormone fibroblast growth factor 21(FGF21)in mediating function of GLP-1RAs in animal models.This was followed by presenting our perspective views.
