**7. Conclusions**

Programming, glucolipotoxicity, and the interactions of ER and oxidative stress in the pathogenesis and maintenance of disease require further unraveling and supporting evidence from clinical studies. Nutritionally and metabolically overloaded beta cells become stressed and inflamed with worsening outcomes for metabolic disease. Beta cell stress and inflammation require further investigation into adaptive mechanisms that evolve to mitigate cellular stress and inflammation, to identify strategies and targets for preserving beta cell physiology.

**Funding:** The author is supported by the National Research Foundation (South Africa).

**Conflicts of Interest:** The authors declare no conflict of interest.
