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The “insulin secretion dual -switch” theory was released, and insulin was regulated by it!丨 Interactive of Professor Yang Jinkui

Experts interviewed | Yang Jinkui Capital Medical University Tongren Hospital

Wen | Jade Sauce

Not long ago, Professor Yang Jinkui, Director of the Department of Endocrinology, Beijing Tongren Hospital affiliated to the Capital Medical University, as a communications author, led the team to publish a “From Hyper-TO Hypoinsulinemia and Diabetes: Effect of Kcnh6 on Insulin Secretion “(from hypertrophy, to low insulin ledmia and diabetes: KCNH6’s effect on insulin secretion). After nearly 10 years of research, the team revealed the mystery of the pathogenesis of diabetes and proposed a new “dual switch” theory.

In the past, I only knew that classic hypoglycemic ages sulfur sulfur drugs can act on the insulin “switch” in the body -Tar β -cell de -potassium potassium channel KATP, thereby promoting insulin secretion. The study of Professor Yang Jinkui found another switch to control insulin secretion -insulin secretion in the body was also adjusted by insulin β -cell complexic potassium potassium channel KCNH6. “Medical community” interviewed Professor Yang Jinkui for this purpose!

Nearly half of people have a large family of diabetes, which has contributed to this study

Professor Yang Jinkui told the “medical community” that diabetes is a very complicated disease. Finding the cause is conducive to the development of new therapy. The current medical technology has a bottleneck in the understanding of such complex diseases, and it is difficult to find a breakthrough. Diabetes has the phenomenon of family gathering. If three generations in a family have diabetes, and the characteristics are more consistent, that is, a diabetic family. Professor Yang realized from many years of clinical practice that “home system” is an important window for the study of diabetes. From this perspective, it will be discovered more intuitive.

In 2009, Professor Yang took a diabetic patient from the mountainous area of ​​Hubei. It is learned from the exchange that the patient was born from a large family of more than 60 people, but four generations in the family have diabetes, and there are also adult hyperglycemia and newborn hypoglycemia. The most surprising thing is that the number of diabetes in this family is as high as 25! Nearly half of the family has diabetes, which has the highest proportion of more than 50 departments. It not only attracted the attention of Professor Yang, but also promoted a new large -scale research bud.

Taking the opportunity of this special diabetes department’s discovery, Professor Yang Jinkui led the team to start data collection and whole genome analysis of nearly 10 years. During the genetic analysis process, the team found that the family’s diabetes may be related to the KCNH6 potassium channel gene, and further verification began: by establishing a mouse diabetes model, let mice simulate the genetic mutations of diabetic patients (including gene knockout and point point of point of genetic knockout and point point The two means of mutation make mice and patients have the same genetic mutations) to see if the mouse model is in line with the characteristics observed in the family department.

Observation results confirmed that both gene mutations mice had had diabetes. KCNH6 gene knockout (KO) or KCNH6 gene P.P235 mutant humanization knocking (Ki) mice’s diabetic phenotype characteristics are consistent with the diabetic patients: initial hypertrophic hypoglycemia with high insulinmia, After adulthood, hyperglycemia and diabetes accompanied by low insulinmia. At this point, the relationship between the genetic and diabetes is affirmed.

The next step of discovering the phenomenon is to demonstrate the mechanism. This mysterious mechanism has also been cracked by Professor Yang Jinkui: Further experiments found that the intracellular calcium concentration of the new KO mice has increased and the secretion of insulin secretion has increased; The phenomenon of β -cell intraocular mesh stress, apoptosis, and decreased insulin secretion. Film clamping studies have found that this is related to the disappearance of the KCNH6 gene P.P235 mutations that cause compound polarization KCNH6 potassium ion channels to disappear. KCNH6 potassium ion channel is the “switch” that controls insulin secretion! Coupled with the “switch” of the known sulfurbal drugs on insulin secretion, this research result is also called “insulin secretion dual switch” theory.

The new theory will guide the research and development of eugenics and new drugs and new drugs

Professor Yang Jinkui said that the significance of this new study is mainly two points. One is to guide eugenics and preferred to prevent diabetes from reappearing in the offspring of patients; the other is to facilitate the development of new drugs. At present, many Chinese medicines have been found to have blood glucose effect, but the specific mechanism has not been studied clearly, and there are certain toxic and side effects in the drugs. The discovery of the new role target can promote the improvement and upgrade of drugs, increase positive effects, and reduce side effects.

For example, some drugs can not only act on the ion channel of islet cells, control insulin secretion, but also act on similar channels for myocardial cells, but at this time, it will be manifested as cardiac toxicity. If drugs can only act on potassium channels secreted by insulin, it can improve efficacy and reduce toxicity. The potassium channels currently discovered are expected to become a new target for diabetic drugs in the future.

Study ideas, or enlighten young scholars

After more than 60 years of sulfurbal hypoglycemic drugs that have been used for more than 60 years, another important switch to control insulin secretion was found, and the “dual switch” theory was naturally a highlight of this study. However, Professor Yang Jinkui also wanted to share a little experience with colleagues, especially young doctors and scholars. Scientific researchers know that after a study has achieved results, a large number of work needs to be carried out in order to implement clinical practice. But in turn, we can also observe phenomena from clinical practice and summarize issues, and use research work to refine rigorous scientific theories. It is through this idea that the “dual switch” theory can be available. Professor Yang Jinkui said that he would encounter various diabetes patients in the clinic, such as the family department of Hubei patients mentioned above. They did not meet the definition of type 1 diabetes. Poor, this is not a typical feature of type 2 diabetes. If it is used as an ordinary patient without further follow -up analysis, major discovery may be missed. Professor Yang keenly locked the family and tried to attack with the “family department” as a breakthrough. In clinical work, young doctors may wish to pay more attention, summarize, and analyze more, and investigate the problem to the end. This will promote human understanding of diseases.

<!-2586: Diabetic terminal page

Future research: focus on “switch” to improve drugs

Next, Professor Yang Jinkui will also lead the team based on the existing research to select insulin “switch” as a new drug target for drug screening, and find more specific drugs with effective drugs and improve natural drugs. A traditional Chinese medicine with hypoglycemic effects has been found, and its active ingredients may work through the KCNH6 potassium channel. The family departments in the study have also doubled from more than 50 at the beginning to more than 100, of which 5 are genetic -related diabetes. The corresponding animal experiments are actively developing.

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