Pancreatic Islet Responses to Metabolic Trauma

Abstract

Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1–2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical anti-psychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets.

Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice

“…Because pancreatic islets expand during states of insulin resistance, 21 we measured insulin-positive cell area, indicative of the pancreatic b-cell population, in response to the corticosterone intervention. Insulin-positive area increased by 2.1-fold in corticosterone-treated mice ( Figure 6, A and B).…”

Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence

“…In healthy individuals, there is a feedback loop between insulin-sensitive tissues and the β-cells in that an increase in peripheral insulin demand is augmented by insulin secretion. Thus, changes in the peripheral insulin sensitivity are reciprocally compensated by changes in circulating insulin levels [ 98 , 99 ]. Failure in this reciprocal loop may result in the disruption of glucose homeostasis and deviations from normal glucose tolerance to the development of glucose intolerance ( Figure 1 ) and, at the extreme, T2DM [ 97 ].…”

Metabolic Syndrome: Major Risk Factor for Morbidity and Mortality in Severely Injured Trauma Patients

“…As a result, insulin insufficiency and pathologic changes in insulin release can develop, which could lead to worse outcomes. 11 For example, Bhayani and colleagues, 12 in their research on MetS and liver resections, found a 5-fold increase in MI, a 2-fold increase in pulmonary complications, and a 70% increase in surgical site infections in patients with the syndrome. We also noted significantly higher rates of acute kidney injury, ARDS, cardiac arrest, decubitus ulcers, MI, unplanned admission to the ICU, unplanned intubations, and severe sepsis in MetS patients.…”

“…The peripheral insulin resistance seen after severe trauma could be opposed by blocking the renin-angiotensin system to improve glucose use in patients already struggling with MetS. 11 In addition, the future of precision medicine in the field of metabolomics has vast potential for these patients. By identifying unique molecular characteristics of a person with MetS at the time of initial trauma, clinicians at the point of care may eventually be able to predict an individual's clinical course, facilitating more timely, individualized treatment, ultimately improving outcomes.…”