Metabolic remodeling triggered by salivation and diabetes in major salivary glands

Abstract

The metabolic profile of major salivary glands was evaluated by C nuclear magnetic resonance isotopomer analysis ( C NMR-IA) following the infusion of [U- C]glucose in order to define the true metabolic character of submandibular (SM) and parotid (PA) glands at rest and during salivary stimulation, and to determine the metabolic remodeling driven by diabetes. In healthy conditions, the SM gland is characterized at rest by a glycolytic metabolic profile and extensive pyruvate cycling. On the contrary, the PA gland, although also dominated by glycolysis, also possesses significant Krebs' cycle activity and does not sustain extensive pyruvate cycling. Under stimulation, both glands increase their glycolytic and Krebs' cycle fluxes, but the metabolic coupling between the two pathways is further compromised to account for the much increased biosynthetic anaplerotic fluxes. In diabetes, the responsiveness of the PA gland to a salivary stimulus is seriously hindered, mostly as a result of the incapacity to burst glycolytic activity and also an inability to improve the Krebs' cycle flux to compensate. The Krebs' cycle activity in the SM gland is also consistently compromised, but the glycolytic flux in this gland is more resilient. This diabetes-induced metabolic remodeling in SM and PA salivary glands illustrates the metabolic need to sustain adequate saliva production, and identifies glycolytic and oxidative pathways as key players in the metabolic dynamism of salivary glands.

Population Based Average Parotid Gland Volume and Prevalence of Incidental Tumors in T1-MRI

“…Higher rates of hyposalivation and microstructural changes of parotid parenchyma have been observed in diabetics. To a lesser extent, this is also the case in the presence of hypertension [ 2 , 22 , 23 , 24 ]. It is unclear whether there is a significant association between prevalence of these diseases and parotid gland size.…”

Efeito do diabete na presença ou ausência da insulina na produção e atividade de enzimas chave do metabolismo energético em glândulas submandibulares de ratos

“…Pesquisas em animais tem permitido o entendimento das mudanças salivares e metabólicas encontradas na disfunção glandular decorrente do DM Sassaki, 1976;Pedroso et al, 1976;Sassaki, 1983;Nicolau et al, 2003;Nicolau et al, 2005;Nogueira et al, 2005b;Nicolau et al, 2006;Leite;Nicolau et al, 2009;Simões et al, 2009;Carvalho, 2017;Ibuki et al, 2020;Souza et al, 2021). Um dos modelos experimentais adotados é o diabete induzido por estreptozotocina.…”

“…Em um estudo em ratos Carvalho, 2017) (Horak;Pritchard, 1971), sintetizar triacilgliceróis, colesterol, fosfolipídios e sulfolipídios (Pritchard, 1967) e verificar a disponibilidade de oxaloacetato mitocondrial Garrett, 1986).…”

“…Uma intrigante diluição da marcação do substrato foi observada em um estudo prévio Carvalho, 2017) aumento nos índices de cárie e doença periodontal, principalmente (Cutando et al, 2003;Manfredi et al, 2004;Mata et al, 2004;Dodds et al, 2005;Teeuw et al, 2010;Al-Rawi, 2011).…”

“…Estudos sobre o metabolismo das glândulas salivares estão associados à regulação da sua secreção (Deutsch;Raper, 1936;Stromblad, 1957;Terroux et al, 1959;Sassaki, 1976;Pedroso et al, 1976). A importância da via glicolítica e do glicogênio para a homeostase glandular já foi demonstrada na literatura científica Cannan, 1922aCannan, ,b, 1923English, 1955;Goldman et al, 1964;Masi et al, 1966;Sassaki, 1976;Pedroso et al, 1976;Nicolau et al, 2003;Nicolau et al, 2005;Carvalho, 2017). Entretanto, embora o significado clínico das glândulas salivares seja bem conhecido, as vias metabólicas que contribuem para sua função ainda precisam ser elucidadas.…”