Gut cells engineered to produce insulin
BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7275.1488/b (Published 16 December 2000) Cite this as: BMJ 2000;321:1488Engineering non-pancreatic cells to produce insulin in response to a glucose load may one day be a successful approach in the treatment of diabetes. Canadian scientists have now shown that cells other than b pancreatic cells can be induced to secrete appropriate levels of insulin in response to eating (Science 2000;290:1959-61).
Dr Anthony Cheung, a researcher in the department of Medicine at the University of Alberta, Canada, believes that a physiologically regulated endogenous supply of insulin will mimic a healthy state better than injections of insulin ever could. But the great challenge for such a gene therapy approach to the treatment of diabetes is to be able to find a way to regulate insulin release that coincides with eating.
Naturally occurring insulin takes a few hours to be manufactured by the pancreas, and in addition to producing the hormone, pancreatic b cells also have the capacity to store insulin and then to secrete it on detection of glucose. Previous attempts at gene therapy have largely concentrated on the manipulation of liver cells, but hepatocytes do not have the ability to store hormones, so the release of insulin is always delayed.
Now Dr Cheung and his team have shown that mice can be genetically engineered to produce human insulin from K cells located in the duodenum. K cells usually produce glucose dependent insulinotropic polypeptide (GIP), so they have an advantage over hepatocytes in that they are already glucose responsive endocrine cells, and already have the correct equipment to be able also to store hormones.
The physiological role of GIPs is that of an anticipatory signal to pancreatic b cells, to increase insulin secretion.
In these studies Dr Cheung showed that when K cells are genetically engineered to produce insulin, normal glucose tolerance can be achieved in animals that have had their own pancreatic b cells ablated. “These genetically engineered K cells produced sufficient amounts of insulin to be able to prevent diabetes developing in these animals,” explained Dr Cheung.
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