Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition

Abstract

Graphical Abstract Highlights d Adipocyte DPP4 contributes to circulating sDPP4, but not to glucose homeostasis d Hepatocyte DPP4 contributes to its circulating activity and hepatic/adipose inflammation d Circulating, soluble DPP4 is markedly induced by systemic DPP4 enzymatic inhibition d DPP4 activity and sDPP4 levels do not correlate with extent of metabolic inflammation

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

“…Dipeptidylpeptidase 4 (DPP4, also known as CD26) was here identified to be deiminated in both llama whole serum and EVs. DPP4 controls glucose homeostasis and has complex roles in inflammation and homeostasis, including in liver cytokine expression, while its activity in plasma has been shown to correlate with body weight and fat mass (Varin et al, 2019). Interestingly, in camel milk, DDP4 inhibitory peptides have been identified and suggested to play roles in the regulation of glycaemia in humans (Nongonierma et al, 2018).…”

Endocrine Conditions and COVID-19

“…Lastly, dipeptidyl peptidase-4 (DPP-4), a surface glycoprotein, which degrades glucagon like peptide 1 ('GLP-1', an incretin hormone), is known to be elevated in DM and obesity [20][21][22], and also functions as a surface receptor for coronaviruses [23,24]. Although the latter is yet to be shown for SARS-CoV-2, the unique role of DPP-4 in coronavirus infections makes DPP-4 inhibition a possible therapeutic target, which may work both by reducing DPP-4 expression and offsetting the cytokine mediated end organ damage [19,25]. This assessment is further strengthened by evidence that DPP-4 inhibition showed anti-inflammatory effects in pre-clinical human studies [19,26,27].…”

“…Although the latter is yet to be shown for SARS-CoV-2, the unique role of DPP-4 in coronavirus infections makes DPP-4 inhibition a possible therapeutic target, which may work both by reducing DPP-4 expression and offsetting the cytokine mediated end organ damage [19,25]. This assessment is further strengthened by evidence that DPP-4 inhibition showed anti-inflammatory effects in pre-clinical human studies [19,26,27]. Taken together, patients with DM may be predisposed to cytokine storms resulting in end organ injury and mortality (▶Fig.…”

“…Importantly, DPP-4 inhibitors and GLP-1 receptor analogues may not only attenuate the chronic inflammatory state in DM but also have independent lung-protective and immunomodulatory effects (in pre-clinical studies) and may prove beneficial (▶ Fig. 3) [19,[69][70][71].…”

“…General COVID-19 precautions for patients with endocrine conditions ▪ All patients should maintain updated contact information for their healthcare ▪ Adequate availability of prescription refills should be ensured ▪ Emergency precautions and sick-day rules should be addressed on all routine clinic visits ▪ Providers should remain up to date with evolving COVID- 19 data and perform a careful critical appraisal of the available and increasing literature to be able to identify high-quality evidence to facilitate informed decisions to individualize care ▪ Elective endocrine clinic visits should be deferred and alternative communication means such as telehealth visits consistent with social distancing should be encouraged ▪ Mailing of prescriptions rather than inperson pickup should be adopted wherever feasible ▪ Patients should be advised to stay updated with recommended vaccinations ▪ Smoking (including hookah/waterpipe) cessation should be advised [165] ▪ Panic buying and stockpiling of medical supplies should be strongly discouraged ▪ Patients should be informed of COVID-19 resources (CDC, WHO websites etc.) to obtain accurate information and follow best practices with respect to COVID-19 (▶Table 2)…”