Science Sub-Journal: SMOC1 is a glucose-reactive liver factor

, diabetes has traditionally been a disease that affects more than 100 million Americans, with only two types of diabetes. But Victoria Salem, a clinical scientist at Imperial College London who was not involved in the study, told the BBC that clinicians were aware that type 1 and type 2 diabetes were "not a very accurate classification" of the disease.To determine a more granular classification, researchers from the Diabetes Center at Lund University in Sweden and the Finnish Institute of Molecular Medicine previously analyzed the medical records and blood of 14,775 patients and studied various diabetes-related indicators, such as long-term blood sugar control, insulin resistance and glycation of hemoglobin, and the genetic association of the disease. Their study revealed five groups of diabetics with different genetic characteristics, complications and disease progression rates.Class 1 (cluster 1) is usually similar to typical type 1 diabetes: when young, other healthy individuals have autoimmune diseases that prevent them from producing insulin, these diseases begin to develop; Patients in category 2 also have the highest risk of retinal lesions; patients in category 3 (cluster 3) have severe insulin resistance, a higher risk of developing diabetic kidney disease (cluster 4) and category 5 (cluster 5), patients in category 4 (cluster 4) have mild obesity-related diabetes, and patients in category 5 (cluster 5) include those with mild age-related diabetes.Inter-tissue communication is a fundamental feature of metabolic regulation, and the liver is at the heart of this process. Hepatokine is a protein secreted by the liver that regulates body metabolism.In a new study, researchers from research institutions such as the University of Melbourne, Monash University, the University of Adelaide and Flinders University in Australia identified spark-related modular calcium binding protein 1 (sparc-related modular calcium-binding protein 1, SMOC1) as a glucose-reactive liver factor and glucose steady-state regulator protein. The findings were recently published in the journal Science Translational Medicine under the title "SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control".Acute celiac injection of SMOC1 improved blood sugar control and insulin sensitivity in mice, but their insulin secretion did not change. SMOC1 inhibits camp (3', 5'-cyclic monophosphate) in the liver - cAMP dependent protein kinase (PKA) - cAMP reaction element binding protein (CREB) signal transducement, resulting in a decrease in glycoglote gene expression, inhibit the liver glucose output, thereby playing its beneficial role in reducing sugar.Excessive expression of SMOC1 in the liver or weekly abdominal injection of stable SMOC1-FC fusion proteins in the liver for four weeks induced a lasting improvement in glucose tolerance and insulin sensitivity in db/db mice, with no adverse effects on fatness, liver tissue pathology or inflammation.In addition, circulating SMOC1 is associated with insulin sensitivity in the liver and body, while in obese, insulin-resistant humans, its levels decrease. Together, these findings identify SMOC1 as a potential drug target for managing blood sugar control in people with type 2 diabetes. (Bio Valley):, Magdalene K. Montgomery et al. SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control. Science Translational Medicine, 2020, doi:10.1126/scitranslmed.aaz8048.