1.
Unique features of β-cell metabolism are lost in type 2 diabetes.
Muñoz, F, Fex, M, Moritz, T, Mulder, H, Cataldo, LR
Acta physiologica (Oxford, England). 2024;:e14148
Abstract
Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell type-specific manner; for instance, the glucose activating hexokinase IV enzyme or Glucokinase (GCK), whereas other genes are selectively "disallowed", including lactate dehydrogenase A (LDHA) and monocarboxylate transporter 1 (MCT1). This selective gene program equips β cells with a unique metabolic apparatus to ensure that nutrient metabolism is coupled to appropriate insulin secretion, thereby avoiding hyperglycemia, as well as life-threatening hypoglycemia. Unlike most cell types, β cells exhibit specialized bioenergetic features, including supply-driven rather than demand-driven metabolism and a high basal mitochondrial proton leak respiration. The understanding of these unique genetically programmed metabolic features and their alterations that lead to β-cell dysfunction is crucial for a comprehensive understanding of T2D pathophysiology and the development of innovative therapeutic approaches for T2D patients.
2.
Monoamines' role in islet cell function and type 2 diabetes risk.
Roberts, FL, Cataldo, LR, Fex, M
Trends in molecular medicine. 2023;(12):1045-1058
Abstract
The two monoamines serotonin and melatonin have recently been highlighted as potent regulators of islet hormone secretion and overall glucose homeostasis in the body. In fact, dysregulated signaling of both amines are implicated in β-cell dysfunction and development of type 2 diabetes mellitus (T2DM). Serotonin is a key player in β-cell physiology and plays a role in expansion of β-cell mass. Melatonin regulates circadian rhythm and nutrient metabolism and reduces insulin release in human and rodent islets in vitro. Herein, we focus on the role of serotonin and melatonin in islet physiology and the pathophysiology of T2DM. This includes effects on hormone secretion, receptor expression, genetic variants influencing β-cell function, melatonin treatment, and compounds that alter serotonin availability and signaling.
3.
Serum cytokine pattern in young children with screening detected coeliac disease.
Björck, S, Lindehammer, SR, Fex, M, Agardh, D
Clinical and experimental immunology. 2015;179(2):230-5
-
-
-
Free full text
Plain language summary
Coeliac disease (CD) is an autoimmune disorder characterised by inflammation in the small bowel after ingesting gluten. Many patients may be asymptomatic and clinically silent, prolonging their diagnosis and treatment. This may put them at risk for long-term complications due to chronic systemic inflammation. Circulating cytokines indicate inflammatory activity in the body and have been shown to be elevated in patients with CD. The aim of this study was to measure the levels of serum cytokines in 26 3-year-old children with CD, both at the time of diagnosis and after starting a gluten-free diet. The findings of this study showed that young children with CD demonstrated elevated levels of serum cytokines at the time of diagnosis. After maintaining a gluten-free diet, many cytokine levels decreased. Based on this study, the authors’ conclude that systemic inflammation due to undiagnosed disease in young children may contribute to long-term complications associated with chronic inflammation, and should be accounted for when screening for the disease.
Abstract
Coeliac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening-detected coeliac disease before and after treatment with a gluten-free diet. Serum samples selected before and after the start of a gluten-free diet from 26 3-year-old children diagnosed with biopsy-proven coeliac disease and from 52 matched controls were assayed in an multiplex enzyme-linked immunosorbent assay (ELISA) for the 10 cytokines: interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13 and tumour necrosis factor (TNF)-α. Among Th1 cytokines, IFN-γ and IL-12p70 were elevated significantly in children with coeliac disease compared to controls (P < 0.001 and P = 0.001, respectively). Similar findings were demonstrated for the Th2 cytokines IL-5 (P < 0.001), IL-10 (P = 0.001) and IL-13 (P = 0.002). No difference in cytokine levels between the two groups was found for TNF-α, IL-1β, IL-2, IL-4 and IL-8. After gluten-free diet, levels of IL-5, IL-12 and IL-10 decreased significantly (P < 0.001, P = 0.002 and P = 0.007) and IFN-γ levels were reduced (P = 0.059). Young children with coeliac disease detected by screening demonstrate elevated levels of serum cytokines at time of diagnosis. A prolonged systemic inflammation may, in turn, contribute to long-term complications known to be associated with untreated coeliac disease.