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Review
. 2020 Jun 9:11:365.
doi: 10.3389/fendo.2020.00365. eCollection 2020.

The Role of the Pentose Phosphate Pathway in Diabetes and Cancer

Tongxin Ge  1 , Jiawen Yang  1 , Shihui Zhou  1 , Yuchen Wang  1 , Yakui Li  1 , Xuemei Tong  1
Affiliations
Review

The Role of the Pentose Phosphate Pathway in Diabetes and Cancer

Tongxin Ge et al. Front Endocrinol (Lausanne). .

Abstract

The pentose phosphate pathway (PPP) branches from glucose 6-phosphate (G6P), produces NADPH and ribose 5-phosphate (R5P), and shunts carbons back to the glycolytic or gluconeogenic pathway. The PPP has been demonstrated to be a major regulator for cellular reduction-oxidation (redox) homeostasis and biosynthesis. Enzymes in the PPP are reported to play important roles in many human diseases. In this review, we will discuss the role of the PPP in type 2 diabetes and cancer.

Keywords: cancer; diabetes; metabolism; obesity; the pentose phosphate pathway.

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Figures

Figure 1
Figure 1
The pentose phosphate pathway (PPP). The PPP branches after the first step of glycolysis and goes back to fructose 6-phosphate and glyceraldehyde 3-phosphate in the glycolytic and gluconeogenic pathway. The PPP produces R5P and NADPH for biosynthesis and redox regulation. Enzymes in the oxidative and non-oxidative PPP are shaded in green.
Figure 2
Figure 2
The role of the PPP in insulin resistance. (A) CARKL is highly expressed in M2 macrophages, limiting the PPP flux by inhibiting G6PD. M2 macrophages release anti-inflammatory mediators including IL-10 and arginase 1 to maintain insulin sensitivity. Decreased G6PD in adipocytes suppresses inflammation and ameliorates insulin resistance. (B) FFAs and pro-inflammatory cytokines including TNF-α, IL-1β, and resistin increase G6PD expression in both adipocytes and M1 macrophages, which stimulate inflammatory responses leading to insulin resistance.
Figure 3
Figure 3
The role of the PPP in insulin secretion. NADPH from the PPP converts oxidized glutathione (GSSG) to reduced glutathione (GSH). GSH elicits insulin granule exocytosis via SENP1. However, NADPH might inhibit insulin secretion by promoting NADPH oxidases (NOXs).
Figure 4
Figure 4
Regulation of G6PD in cancers. Several signaling pathways have been identified to be responsible for promoting G6PD expression or activity in cancer cells. These signaling pathways interact with each other, adding complexity to the regulation of G6PD.
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