Dataset Information

Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

ABSTRACT: Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

SUBMITTER: Sumida Y

PROVIDER: S-EPMC7404115 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Sumida Yoshio Y Yoneda Masashi M Toyoda Hidenori H Yasuda Satoshi S Tada Toshifumi T Hayashi Hideki H Nishigaki Yoichi Y Suzuki Yusuke Y Naiki Takafumi T Morishita Asahiro A Tobita Hiroshi H Sato Shuichi S Kawabe Naoto N Fukunishi Shinya S Ikegami Tadashi T Kessoku Takaomi T Ogawa Yuji Y Honda Yasushi Y Nakahara Takashi T Munekage Kensuke K Ochi Tsunehiro T Sawada Koji K Takahashi Atsushi A Arai Taeang T Kogiso Tomomi T Kimoto Satoshi S Tomita Kengo K Notsumata Kazuo K Nonaka Michihiro M Kawata Kazuhito K Takami Taro T Kumada Takashi T Tomita Eiichi E Okanoue Takeshi T Nakajima Atsushi A Japan Study Group Of Nafld Jsg-Nafld

International journal of molecular sciences 20200713 14

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic ne ...[more]

PMID: 32668632

Similar Datasets

Project description:BackgroundType 2 diabetes is characterized by insulin resistance accompanied by defective insulin secretion. Transgenic mouse models play an important role in medical research. However, single transgenic mouse models may not mimic the complex phenotypes of most cases of type 2 diabetes.MethodsFocusing on genes related to pancreatic islet damage, peripheral insulin resistance and related environmental inducing factors, we generated single-transgenic (C/EBP homology protein, CHOP) mice (CHOP mice), dual-transgenic (human islet amyloid polypeptide, hIAPP; CHOP) mice (hIAPP-CHOP mice) and triple-transgenic (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1; hIAPP; CHOP) mice (11β-HSD1-hIAPP- CHOP mice). The latter two types of transgenic (Tg) animals were induced with high-fat high-sucrose diets (HFHSD). We analyzed the diabetes-related symptoms and histology features of the transgenic animals.ResultsComparing symptoms on the spot-checked points, we determined that the triple-transgene mice were more suitable for systematic study. The results of intraperitoneal glucose tolerance tests (IPGTT) of triple-transgene animals began to change 60 days after induction (p < 0.001). After 190 days of induction, the body weights (p < 0.01) and plasma glucose of the animals in Tg were higher than those of the animals in Negative Control (Nc). After sacrificed, large amounts of lipid were found deposited in adipose (p < 0.01) and ectopically deposited in the non-adipose tissues (p < 0.05 or 0.01) of the animals in the Tg HFHSD group. The weights of kidneys and hearts of Tg animals were significantly increased (p < 0.01). Serum C peptide (C-P) was decreased due to Tg effects, and insulin levels were increased due to the effects of the HFHSD in the Tg HFHSD group, indicating that damaged insulin secretion and insulin resistance hyperinsulinemia existed simultaneously in these animals. The serum corticosterone of Tg was slightly higher than those of Nc due to the effects of the 11βHSD-1 transgene and obesity. In Tg HFHSD, hepatic adipose deposition was more severe and the pancreatic islet area was enlarged under compensation, accompanying apoptosis. In the transgenic control diet (Tg ControlD) group, hepatic adipose deposition was also severe, pancreatic islets were damaged, and their areas were decreased (p < 0.05), and apoptosis of pancreatic cells occurred. Taken together, these data show the transgenes led to early-stage pathological changes characteristic of type 2 diabetes in the triple-transgene HFHSD group. The disease of triple-transgenic mice was more severe than that of dual or single-transgenic mice.ConclusionThe use of multi-transgenes involved in insulin resistance and pancreatic apoptosis is a better way to generate polygene-related early-stage diabetes models.

Dataset Information

Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Publications

Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets