Is islet function expected to be reversed? Review of the 2022 Diabetic Islet Regulation and Regenerative Medicine Conference of the Diabetes Branch of the Chinese Medical Association

Professor Xu Xiangjin pointed out that in recent years, T1DM cell therapy has made many breakthroughs and inspiring results, such as induced pluripotent stem cells, autoperipheral hematopoietic stem cells, mesenchymal stem cells, stem cell exosomes, etc.
, which provide new ideas
for the future individualized staged precision treatment of T1DM.
However, islet transplantation is currently only for a small number of T1DM patients with absolute indications, and stem cell therapy technology is still in the clinical research stage, and cell therapy cannot be widely carried out
as a routine clinical practice.
In the future, with the continuous optimization of stem cell therapy related technologies, the gradual improvement of treatment safety and efficacy, and the accumulation of clinical evidence-based evidence, stem cells are expected to be more widely used in the clinical treatment of T1DM, bringing good news
to the majority of patients.


Professor Gu Weiqiong of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine introduced the research progress
of autologous hematopoietic stem cell therapy for type 1 diabetes jointly completed by Ruijin Hospital and Nanjing Gulou Hospital using type 1 diabetes as an example.
Insulin consumption was significantly reduced at 1 month after stem cell transplantation, reaching a minimum at 3 months postoperatively, and remained at a low level
for 24 months.
From the research point of view, hematopoietic stem cell transplantation is relatively safe for the treatment of diabetes, and the vast majority of patients benefit
from it.


Professor Wang Dan of Heilongjiang Provincial Hospital introduced the current situation and progress
of islet cell transplantation.
Clinical studies have confirmed that allogeneic islet cell transplantation can improve HbA1c in patients, make some patients stop insulin for several years, reduce the occurrence of hypoglycemia, and improve diabetic nephropathy and eye disease
.
However, insufficient donor sources, immunosuppressive therapy, and long-term survival of transplanted cells all restrict clinical promotion
.


Professor Chen Hong of Zhujiang Hospital affiliated to Southern Medical University analyzed the new targets and new hopes
for diabetes treatment from α-cells and glucagon.
When insulin is resistant, α cells secrete more glucagon, exacerbating the progression
of diabetes.
Therefore, reprogramming of pancreatic islet α cells can promote the remission
of diabetes.
Basic studies have found that the use of GCGR can promote α cell proliferation and increase β cell mass in diabetic mice, and LY3437943 (a novel triple-receptor agonist) can reduce body weight and control blood sugar through this mechanism, but its effect on stimulating α cell proliferation decreases
with age.
In the future, the development of GCGR-related therapeutic drugs is worth looking forward to
.


Professor Wei Rui of Peking University Third Hospital combined the research results of the team to elaborate the role of pancreatic islet α cells in the regulation and regeneration of
β cell function.
Studies have found that blocking the glucagon pathway can reduce blood glucose in a variety of T1D and T2D model animals and patients, and islet-α cell-mediated liver/gut-pancreatic dialogue is involved in the regulation
of islet function.
The secretion of islet-α cytokines is self-regulated, and promoting the production of GLP-1 by α cells is an important way to β cell protection, and inducing the transformation of α to β cells is an important way
to regenerate islets.


Dr.
Du Yuanyuan of Peking University Stem Cell Center reported on the research progress
of Professor Deng Hongkui's research group in the treatment of diabetes with human pluripotent stem cells.
The researchers found that on a diabetic model monkey with large blood sugar fluctuations and poor overall control, the blood glucose control was significantly improved
after transplantation of islet cells differentiated from human pluripotent stem cells.
This result suggests that islet cell transplantation differentiated by human pluripotent stem cells is expected to be used in the treatment of patients with fragile diabetes, but there is still a gap between the components and functions of human pluripotent stem cells and islets isolated from humans, and the long-term safety remains to be observed
.


Professor Hou Xu of Shandong Provincial Hospital took a different approach and revealed the significance
of spatial heterogeneity of adipose stem cells in diet-induced obesity through mass spectrometry flow cytometry.
The study found that there were tissue-specific cell populations in subcutaneous and visceral fat in mice, in which the CD142+ subpopulation in VAT significantly increased the proportion in the high-fat diet-induced obesity model, and liraglutide was able to reduce the proportion of
cells in this population.
The proportion of CD26+ subsets in SAT was significantly reduced in the high-fat diet-induced obesity model, and liraglutide was able to increase the proportion of
cells in this population.
This means that the heterogeneity of different stem cell subsets in adipogenic differentiation potential provides a new direction
for exploring obesity therapeutic targets.


Professor Yu Miao of Peking Union Medical College Hospital gave a report
on "The effect of new hypoglycemic drugs on the function and regeneration of pancreatic islet Beta cells".
The protective effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on islet β cells has been fully confirmed in animal experiments, and the results of some recent clinical trials of new hypoglycemic drugs have confirmed their great application prospects
in improving the function of pancreatic islet β cells in multiple dimensions (including islet β cell sensitivity to glucose, insulin secretion ability, etc.
) and alleviating insulin resistance.