Open the "New Door" of Diabetes Treatment!

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100 years ago, the discovery of insulin opened the door to life and hope for millions of people with diabetes
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Since then, insulin has been considered the mainstay of treatment for hyperglycemic disorders such as diabetes
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Today, 100 years later, scientists from Salk have discovered that a substance produced in adipose tissue - exogenous fibroblast growth factor 1 (FGF1) - acts as quickly and efficiently as insulin.
Regulate blood sugar
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Some scholars believe that this discovery may lead to the development of new strategies for diabetes treatment, and also lays the foundation for exploring new ways of metabolism
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Figure 1 PDE3B pathway (insulin) and newly discovered PDE4 (FGF1) pathway Important discovery! FGF1 regulates blood sugar by inhibiting lipolysis.
On January 4, 2022, a study titled "FGF1 and insulin control lipolysis by convergent pathways" was published in the journal Cell Metabolism.
The hormone FGF1 is able to regulate blood sugar by inhibiting the breakdown of fat (lipolysis)
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Like insulin, FGF1 controls blood sugar by inhibiting lipolysis, but the two hormones work in different ways
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Importantly, this difference may allow FGF1 to more safely and successfully lower blood sugar in insulin-resistant patients
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"Finding a second hormone that inhibits lipolysis and lowers blood sugar is a scientific breakthrough," said co-author Ronald Evans, professor of molecular developmental biology.
This will help us understand how energy stores are managed in the body
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" Professor Ronald Evans When we eat, energy-rich fats and glucose enter the bloodstream
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Insulin normally delivers these nutrients to cells in muscle and fat tissue for immediate use or storage for later use
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In people with insulin resistance, glucose cannot be removed from the blood efficiently, and more rapid lipolysis increases blood fatty acid levels
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The extra fatty acids accelerate the production of glucose in the liver, leading to further increases in glucose levels
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In addition, accumulation of fatty acids in organs can exacerbate the development and progression of insulin resistance in diabetes and obesity
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 Previously, laboratory studies showed that injecting FGF1 significantly lowered blood sugar levels in mice, and chronic FGF1 treatment alleviated insulin resistance, but how it works consistently has been a mystery
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The research team investigated the mechanisms behind these phenomena and the connections between them
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First, they found that FGF1, like insulin, inhibits lipolysis
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It was further found that FGF1, like insulin, regulates hepatic glucose production
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These similarities led the team to wonder whether FGF1 and insulin use the same signaling (communication) pathway to regulate blood sugar
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 Explore in depth! A second glycemic regulatory pathway other than insulin - PDE4 It is well known that insulin inhibits lipolysis through PDE3B
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Considering that PDE3B is an enzyme that initiates a signaling pathway, the team tested a series of similar enzymes for this purpose
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They were surprised to find that FGF1 uses a different pathway -- PDE4
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 "This mechanism can be counted as a second circulation pathway, with all the advantages of a parallel pathway
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In insulin resistance, insulin signaling is affected
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However, by using different signaling cascades, it is guaranteed that one does not work in one of them.
In other words, the new pathway still controls lipolysis and regulates blood sugar
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" said study first author Gencer Sankar, a postdoctoral researcher in Evans' lab.
Sancar) said
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Figure 2 The regulatory mechanism of insulin and FGFR1 Looking forward to the future! The discovery of the PDE4 pathway for the new treatment of diabetes has opened up a new path for the development of new drugs and basic research related to hyperglycemia/insulin resistance
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On the one hand, scientists are working hard to improve the activity of PDE4 by modifying FGF1; on the other hand, they are trying to target and activate the upstream signaling pathway of PDE4
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 "The unique ability of FGF1 to induce a sustained drop in blood sugar in insulin-resistant diabetic mice is a promising new avenue for diabetes treatment
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In the future, we hope to gain a deeper understanding of this pathway and find out how it contributes to energy in the body.
More roles in the balance and how to manipulate it can ultimately lead to better options for diabetes treatment," said Michael Downes, a senior staff scientist in the Evans lab
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Reference: [1]SALK INSTITUTE.
Salk researchers find a new route for regulating blood sugar levels independent of insulin New molecular pathway controls blood glucose, circumventing insulin resistance[EB/OL].
2022-1-4.
https://www .
salk.
edu/news-release/salk-researchers-find-a-new-route-for-regulating-blood-sugar-levels-independent-of-insulin/.
[2]https://doi.
org/10.
1016 /j.
cmet.
2021.
12.
004