Pancreas Transplantation
Jack L. Leahy, Nathaniel G. Clark, William T. Cefalu in Medical Management of Diabetes Mellitus, 2000
The goal of pancreas and islet transplantation is to provide a full complement of insulin-secreting pancreatic beta ceUs to a recipient with type 1 diabetes. This seemingly simple task is complicated by the complex structural and physiological relations present in the pancreas. The beta cells are the predominant cell type found in pancreatic islets, and they represent about 1% of the total pancreatic mass. The remaining 99% of the pancreas is composed of exocrine tissue that secretes digestive enzymes into the small intestine. Islets are composed of beta cells and three other types of endocrine cells: the glucagon-secreting alpha cell, the somatostatin-secreting delta cell, and the pancreatic polypeptide-secreting pp cell. To accomplish the goal of replacing the beta cells in a patient with type 1 diabetes, transplantation of isolated beta cells, isolated islets, or unmanipulated pancreatic tissue could be considered. The techniques necessary to isolate beta cells from the other islet cells have not yet been sufficiently well developed to render beta cells suitable for human transplantation. Isolation of functional islets from the exocrine tissue has been successfully performed for more than a decade, but survival of transplanted islets has been difficult to achieve. Consequently, insertion of unmanipulated pancreatic tissue has been and remains the transplant procedure of choice for patients with type 1 diabetes.
INTRODUCTION
David M. Gibson, Robert A. Harris in Metabolic Regulation in Mammals, 2001
the beta cells of the endocrine pancreas). Levels of the many hormones that circulate through all tissues are tightly regulated (basal or diurnal "set-point" patterns). A rise (or fall) in the concentration of a particular endocrine hormone is a signal sensed only by а specific receptor on the plasma membrane of a limited set of cell types. (Some receptors lie within cells.) The stereospecific binding of the signal ligand elicits a sequence of molecular changes in the responding cell (signal transduction) that target effector proteins designen! to carry out the specialized functions of the cell. Depending on the cell type this is manifested as the secretion of a cell product (e.g. other hormones or locally activc paracrines); initiation ol a cell cycle; the synthesis or release ol storage metabolic fuels; contraction or movement of a cell; the blockage or conveyance of a wave of depo larization in a neuron, or even the programmed death of a cell (apoptosis) (Chapter }). As with the neuromuscular automaton all of these signaled events are orchestrated in the context of the response of the organism to its environment, as well as maintaining its internal, global homeostasis (e.g. caloric homeostasis of metabolic fuels in the blood). Both levels of sensitivity and response in the final analysis are dedicated to the well being of the constituent, captive cells of the multicellular organism.
Mitochondrial Dysfunction in Diabetes
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
A balance between gastrointestinal tract, uptake and utilization in peripheral muscle and adipose tissue, and glucose production by the liver are a summary of multiple tissue specific mechanisms of blood glucose homeostasis. These processes are normally tightly regulated by different hormones, including insulin, glucagon, amylin, and gut incretins. Uptake and regulation of substrates into cells is mediated by insulin for ATP generation. Beta cells in the pancreas respond to an increase in blood glucose by secreting insulin, allowing uptake of glucose into the cell, ultimately leading to utilization of glucose, while decreasing gluconeogenesis and driving glucose storage in the liver. Glucagon is secreted from pancreatic alpha cells responding to lower glucose levels in the blood, which in turn increases glycogen breakdown and gluconeogenesis in the liver. In other insulin sensitive tissues, such as adipose tissue and muscle, decreased glucose uptake occurs in response to glucagon (21–26).
The Relationship between the Lipid Accumulation Product and Beta-cell Function in Korean Adults with or without Type 2 Diabetes Mellitus: The 2015 Korea National Health and Nutrition Examination Survey
Published in Endocrine Research, 2022
Hye Eun Cho, Seung Bum Yang, Mi Young Gi, Ju Ae Cha, so Young Park, Hyun Yoon
Insulin resistance and beta cell dysfunction contribute to the development of T2DM.34 Pancreatic beta cells are the secretory cells that release insulin, an essential hormone regulating lipid and glucose metabolism. Excessive lipid accumulation causes detrimental effects on non-adipose tissues, such as skeletal muscle, liver, heart, kidney, and pancreatic beta cells.26,35 Lipotoxicity due to excessive lipid accumulation can contribute to beta-cell dysfunction and death by the generation of intracellular cytotoxic metabolites, such as free fatty acids, oxidative stress, glucolipotoxicity, and endoplasmic reticulum stress.36–38 In the context of lipid accumulation and beta-cell function, free fatty acids acutely increase glucose-stimulated insulin secretion through cell surface receptors and intracellular pathways.39 However, chronic exposure to free fatty acids, combined with elevated glucose (glucolipotoxicity), can impair the function and viability of beta cells.40
Melatonin promotes self-renewal of nestin-positive pancreatic stem cells through activation of the MT2/ERK/SMAD/nestin axis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
A key functional feature of beta cells is its ability to repeatedly perform glucose-stimulated insulin secretion. Beta cells challenged sequentially with 5.5, 20.5, 5.5, 20.5, 5.5 and 20.5 mM glucose, with a 30 min incubation for each concentration. After sequential low/high-glucose challenges, insulin concentration were analyzed in supernatant using ELISA. And glucose-induced insulin secretion demonstrated that PSCs derived from beta cells could release insulin at glucose concentrations of 5.5 mM and 20.5 mM. Analysis of glucose-induced insulin secretion demonstrated that beta cells derived with different combinations of inducers could release insulin, while undifferentiated progenitor cells (G1) did not release insulin. The box plots show that insulin secretion increased when the glucose concentration increased in G2–G7, when the secreted insulin amounts of IPCs differentiation from PSCs was assessed, the combination of nicotinamide, HGF, and active-A-induced IPCs secretion at a higher efficiency compared with combinations of melatonin (Figure 10). These validation results were largely in agreement with the data of IPCs differentiation.
Type 2 diabetes mellitus and cardiovascular disease: focus on the effect of antihyperglycemic treatments on cardiovascular outcomes
Published in Expert Review of Cardiovascular Therapy, 2020
Ravi Choxi, Sumon Roy, Angeliki Stamatouli, Stéphanie B Mayer, Ion S Jovin
The pathophysiology of DM2 is complex, with the crux being a combination of both insulin resistance and relative insulin deficiency [4]. Multiple molecular feedback loops maintain glucose homeostasis. Insulin is secreted in response to glucose sensing by the beta cells. The release of insulin mediates the uptake of glucose, amino acids, and fatty acids by insulin-responsive tissues [4]. Insulin resistance is multifactorial in origin, most commonly in a setting of obesity due to the central accumulation of adipose tissue, especially at the level of the liver, leading to unsuppressed gluconeogenesis, as well as frequently iatrogenically through the prescription of obesogenic agents [5,6]. Insulin resistance then results in increased circulating blood glucose levels, which further exacerbate beta-cell dysfunction via glucose-toxicity. The mechanisms underlying insulin production, secretion, and resistance are affected by multiple genetic and environmental causes [7].
Related Knowledge Centers
- Amylin
- Diabetes
- Glucose
- Endocrine System
- Insulin
- Cell
- Pancreatic Islets
- Hormone
- Endoplasmic Reticulum
- C-Peptide