Reduced glucose‐induced insulin secretion in low‐protein‐fed rats is associated with altered pancreatic islets redox status

Abstract

In the present study, we investigated the relationship between early life protein malnutritioninduced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H 2 O 2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H 2 O 2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement.Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H 2 O 2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H 2 O 2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine. K E Y W O R D Santioxidant enzymes, insulin secretion, pancreatic islets, protein malnutrition, reactive oxygen species | INTRODUCTIONInsulin release is known to be tightly coupled to ATP production.Briefly, the canonical theory of glucose-induced insulin secretion (GIIS) states that when blood glucose rises, islet β-cells stimulate ATP synthesis. ATP acts on ATP-dependent K + channels leading to membrane depolarization. This process is followed by opening of voltage-sensitive calcium channels; increasing cytosolic Ca 2+ concentration and, consequently, insulin exocytosis (Aguilar-Bryan et al., 1995).Although not yet fully understood, the discovery of ATP-independent K + channels mechanisms gave rise to several speculations about how glucose metabolism could regulate GIIS in addition to the solely ATP enhancement effect (Szollosi, Nenquin, Aguilar-Bryan, Bryan, & Henquin, 2007

Involvement of M1 and M3 receptors in isolated pancreatic islets function during weight cycling in ovariectomized rats

“…Plasma estradiol levels in females may be endangered from insulin deficiency by inhibiting oxidative stress (Yokomizo et al, 2014). The susceptibility of pancreatic islets to oxidative stress is credited to their low level of expression of antioxidant enzymes (Lenzen et al 1996) such as SOD1 (Cappelli et al 2018), SOD2 (superoxide dismutase 1,2) and catalase (Takahashi et al 2014). The genetic association of SOD2 with type II diabetes has been described (Miao et al 2009).…”

Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway

“…Previous studies reported changes in antioxidant enzymes activity and reactive oxygen species concentration in islets from protein malnourished rodents [16,17]. However, studies investigating the effects of amino acid restriction on beta cell viability are still scarce.…”

Pyrroloquinoline quinone regulates the redox status in vitro and vivo of weaned pigs via the Nrf2/HO-1 pathway

“…Oxidative stress leads to many diseases, such as sepsis and enteritis, in young animals [1,2]. Earlyweaned pigs suffer oxidative challenges that produce large amounts of reactive oxygen species (ROS) [3].…”