Insulin Suppresses Its Own Secretion In Vivo

Argoud, G. M.; Schade, David S.; Eaton, R. Philip

doi:10.2337/diab.36.8.959

Cited by 95 publications

(24 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In healthy volunteers, exogenous insulin administration suppressed c-peptide release during normoglycemia [12, 13]. This suppressive effect was, however, attenuated during mild hyperglycemia in subjects with non-insulin dependent diabetes [14].…”

Section: Discussionmentioning

confidence: 99%

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

Crisman

Lucchetta

Luethi

et al. 2017

Ann. Intensive Care

View full text Add to dashboard Cite

BackgroundIn critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aimed to explore this effect in patients with type 2 diabetes.MethodsWe prospectively enrolled a cohort of 45 critically ill patients with type 2 diabetes managed according to a liberal glucose protocol (target blood glucose 10–14 mmol/l). We recorded the administration of insulin and oral hypoglycemic agents and measured plasma c-peptide as surrogate marker of endogenous insulin secretion on the first two consecutive days in ICU.ResultsOverall, 20 (44.4%) patients required insulin to achieve target blood glucose. Insulin-treated patients had higher glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and greater blood glucose levels but lower c-peptide levels on admission. Premorbid insulin-requiring diabetes was independently associated with lower admission c-peptide, whereas greater plasma creatinine was independently associated with higher levels. Increases in c-peptide were positively correlated with an increase in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r = 0.56, P = 0.004) receive insulin. However, insulin administration was independently associated with a greater increase in c-peptide (P = 0.04). This association was not modified by the use of oral insulin secretagogues.ConclusionsC-peptide, a marker of beta-cell response, responds to and is influenced by glycemia and renal function in critically ill patients with type 2 diabetes. In addition, in our cohort, exogenous insulin administration was associated with a greater increase in c-peptide in response to hyperglycemia. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12615000216516).Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0274-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

Crisman

Lucchetta

Luethi

et al. 2017

Ann. Intensive Care

View full text Add to dashboard Cite

show abstract

“…Similarly, early intensive insulin therapy with multiple injections or continuous subcutaneous insulin infusion in subjects with newly diagnosed T2DM has favorable outcomes in terms of recovery and maintenance of beta cell function (especially restoration of acute insulin response) (91). The exact mechanisms behind the beneficial effects of exogenous insulin administration on beta cells are not completely elucidated, but it is though that it allows cells rest, at least in part by down-regulating their metabolism and/or by releasing them from the hyperglycemic stress (92). Insulin therapy may also protect pancreatic beta cells by decreasing the severity of insulitis, suppressing the inflammatory processes, reducing antigen expression and subsequent amelioration of T cell responses/number of infiltrative cells in the islets (93).…”

Section: Clinical Considerationsmentioning

confidence: 99%

Diabetes and beta cell function: from mechanisms to evaluation and clinical implications

2013

View full text Add to dashboard Cite

Diabetes is a complex, heterogeneous condition that has beta cell dysfunction at its core. Many factors (e.g. hyperglycemia/glucotoxicity, lipotoxicity, autoimmunity, inflammation, adipokines, islet amyloid, incretins and insulin resistance) influence the function of pancreatic beta cells. Chronic hyperglycaemia may result in detrimental effects on insulin synthesis/secretion, cell survival and insulin sensitivity through multiple mechanisms: gradual loss of insulin gene expression and other beta-cell specific genes; chronic endoplasmic reticulum stress and oxidative stress; changes in mitochondrial number, morphology and function; disruption in calcium homeostasis. In the presence of hyperglycaemia, prolonged exposure to increased free fatty acids result in accumulation of toxic metabolites in the cells (“lipotoxicity”), finally causing decreased insulin gene expression and impairment of insulin secretion. The rest of the factors/mechanisms which impact on the course of the disease are also discusses in detail.The correct assessment of beta cell function requires a concomitant quantification of insulin secretion and insulin sensitivity, because the two variables are closely interrelated. In order to better understand the fundamental pathogenetic mechanisms that contribute to disease development in a certain individual with diabetes, additional markers could be used, apart from those that evaluate beta cell function.The aim of the paper was to overview the relevant mechanisms/factors that influence beta cell function and to discuss the available methods of its assessment. In addition, clinical considerations are made regarding the therapeutical options that have potential protective effects on beta cell function/mass by targeting various underlying factors and mechanisms with a role in disease progression.

show abstract

“…Hence, the effect of dialysis on u en cannot be defined patient-specifically by the model without added data that was not available in this study. Alternatively, it has been reported that endogenous insulin secretion is also affected by exogenous insulin [38]. As plasma insulin levels are suspected to decrease during dialysis, it is suspected that endogenous insulin secretion would increase at a cohort level.…”

Section: Discussionmentioning

confidence: 99%

Impact of Haemodialysis on Insulin Kinetics of Acute Kidney Injury Patients in Critical Care

2015

View full text Add to dashboard Cite

Critically ill patients are occasionally associated with an abrupt decline in renal function secondary to their primary diagnosis. The effect and impact of haemodialysis (HD) on insulin kinetics and endogenous insulin secretion in critically ill patients remains unclear. This study investigates the insulin kinetics of patients with severe acute kidney injury (AKI) who required HD treatment and glycaemic control (GC). Evidence shows that tight GC benefits the onset and progression of renal involvement in precocious phases of diabetic nephropathy for type 2 diabetes. The main objective of GC is to reduce hyperglycaemia while determining insulin sensitivity. Insulin sensitivity (SI) is defined as the body response to the effects of insulin by lowering blood glucose levels. Particularly, this study used SI to track changes in insulin levels during HD therapy. Model-based insulin sensitivity profiles were identified for 51 critically ill patients with severe AKI on specialized relative insulin nutrition titration GC during intervals on HD (OFF/ON) and after HD (ON/OFF). The metabolic effects of HD were observed through changes in SI over the ON/OFF and OFF/ON transitions. Changes in model-based SI at the OFF/ON and ON/OFF transitions indicate changes in endogenous insulin secretion and/or changes in effective insulin clearance. Patients exhibited a median reduction of −29 % (interquartile range (IQR): [−58, 6 %], p = 0.02) in measured SI after the OFF/ON dialysis transition, and a median increase of +9 % (IQR −15 to 28 %, p = 0.7) after the ON/OFF transition. Almost 90 % of patients exhibited decreased SI at the OFF/ON transition, and 55 % exhibited increased SI at the ON/OFF transition. Results indicate that HD commencement has a significant effect on insulin pharmacokinetics at a cohort and per-patient level. These changes in metabolic behaviour are most likely caused by changes in insulin clearance or/and endogenous insulin secretion.

show abstract

Insulin Suppresses Its Own Secretion In Vivo

Cited by 95 publications

References 21 publications

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

Diabetes and beta cell function: from mechanisms to evaluation and clinical implications

Impact of Haemodialysis on Insulin Kinetics of Acute Kidney Injury Patients in Critical Care

Contact Info

Product

Resources

About