Prevalence of Residual Beta-cell Function in Insulin-Dependent Diabetics in Relation to Age at Onset and Duration of Diabetes

Madsbad, Sten; Faber, O. K.; Binder, Chr.; McNair, Peter; Christiansen, C.; Transbøl, Ib

doi:10.2337/diab.27.1.s262

Cited by 103 publications

(59 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several hypotheses have been expounded to account for hyperglucagonemia in people with diabetes. Type 1 and type 2 diabetes are both characterized by a deficit in ␤-cell mass (7)(8)(9)(10)(11) and impaired postprandial insulin secretion (6,12,13). This is consistent with the role of the deficient intraislet insulin on postprandial suppression of glucagon secretion (14 -16).…”

supporting

confidence: 68%

Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion

Meier¹,

Kjems²,

Veldhuis

et al. 2006

Diabetes

131

View full text Add to dashboard Cite

Type 2 diabetes is characterized by an ϳ60% loss of ␤-cell mass, a marked defect in postprandial insulin secretion, and a failure to suppress postprandial glucagon concentrations. It is possible that postprandial hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin secretion. To address this, we studied eight adult Goettingen minipigs before and after an ϳ60% reduction in ␤-cell mass induced by alloxan. Pigs were studied fasting and after ingestion of a mixed meal. Insulin and glucagon secretion were determined by deconvolution of blood hormone concentrations measured at 1-min intervals. The relationship between insulin and glucagon release was analyzed using cross-correlation and forward versus reverse cross-approximate entropy. We report that glucagon and insulin were secreted in ϳ4-min pulses. Prealloxan, postprandial insulin secretion drove an ϳ20% suppression of glucagon concentrations (P < 0.01), through inhibition of glucagon pulse mass. The alloxan-induced ϳ60% deficit in ␤-cell mass lead to an ϳ70% deficit in postprandial insulin secretion and loss of the postprandial insulindriven suppression of glucagon secretion. We conclude that postprandial hyperglucagonemia in type 2 diabetes is likely due to loss of intraislet postprandial suppression of glucagon secretion by insulin. Diabetes 55: [1051][1052][1053][1054][1055][1056] 2006 H yperglucagonemia is a characteristic of both type 1 and type 2 diabetes (1-3). In the overnight-fasted state, plasma glucagon concentrations in patients with diabetes are often comparable to those of nondiabetic individuals but are inappropriately high in the setting of hyperglycemia (1). After glucose ingestion, there is impaired glucagon suppression in both type 1 and type 2 diabetes (4,5). Postprandial hyperglucagonemia is an important contributor to failed suppression of hepatic glucose release after meal ingestion (3,6). Several hypotheses have been expounded to account for hyperglucagonemia in people with diabetes. Type 1 and type 2 diabetes are both characterized by a deficit in ␤-cell mass (7-11) and impaired postprandial insulin secretion (6,12,13). This is consistent with the role of the deficient intraislet insulin on postprandial suppression of glucagon secretion (14 -16).To address this, we studied a porcine model of type 2 diabetes with an alloxan-induced ϳ60% deficit in ␤-cell mass (17). We measured, in 1-min intervals, circulating insulin and glucagon concentrations in the fasting state and then after ingestion of a mixed meal in the same pigs before and after the alloxan-induced reduction of ␤-cell mass. We analyzed these data to address the following questions: 1) Is glucagon secreted in pulses, and if so, are these pulses modulated to regulate glucagon secretion? 2) After ingestion of a mixed meal, does insulin secretion contribute to suppression of glucagon secretion? 3) Does an ϳ60% decrease in ␤-cell mass lead to impaired insulinmediated suppression of glucagon secretion? RESEARCH DESIGN AND METHODSInsulin secretion in relation ...

show abstract

supporting

confidence: 68%

Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion

Meier¹,

Kjems²,

Veldhuis

et al. 2006

Diabetes

131

View full text Add to dashboard Cite

show abstract

“…A significant subset of patients with type 1 diabetes continue to produce Cpeptide, years after their diagnosis [4][5][6][7][8]. Moreover, pancreatic cells staining for insulin are generally reported by autopsy studies of patients with long-term type 1 diabetes [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Beta cell function during rapamycin monotherapy in long-term type 1 diabetes

Piemonti¹,

Maffi²,

Monti³

et al. 2010

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Type 1 diabetes is considered nonreversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function in patients with long-term type 1 diabetes. Methods We examined pancreatic beta cell function in 22 patients with long-term type 1 diabetes (median disease duration 27 years), who had been receiving rapamycin monotherapy (0.1 mg/kg; target trough levels 8-10 ng/ml; 26-314 days) as pre-conditioning for islet transplantation. As control, beta cell function was measured in 14 patients (median disease duration 17 years) who were waiting for an islet transplant without rapamycin pre-conditioning.

show abstract

“…In reviewing reports on the islet pathology in human diabetes, we noticed that not all ␤-cells were equally affected by the pathogenic process (3). At clinical onset, a large proportion of ␤-cells had indeed disappeared, but all cases still exhibited functional ␤-cells (3,4). Beyond the first year after onset, virtually no ␤-cells were left in patients younger than 7 years of age, but this was not as common in older individuals; when onset was diagnosed above the age of 20 years, long-term persistence of ␤-cells was rather the rule than the exception (3).…”

mentioning

confidence: 99%

Role of pancreatic beta-cells in the process of beta-cell death.

et al. 2001

View full text Add to dashboard Cite

Studies on the pathogenesis of type 1 diabetes have mainly focused on the role of the immune system in the destruction of pancreatic beta-cells. Lack of data on the cellular and molecular events at the beta-cell level is caused by the inaccessibility of these cells during development of the disease. Indirect information has been collected from isolated rodent and human islet cell preparations that were exposed to cytotoxic conditions. This article reviews in vitro experiments that investigated the role of beta-cells in the process of beta-cell death. beta-Cells rapidly die in necrosis because of toxic levels of oxidizing radicals or of nitric oxide; they progressively become apoptotic after prolonged culture at low glucose or with proinflammatory cytokines. Their susceptibility to necrosis or apoptosis varies with their functional state and thus with the environmental conditions. A change in cellular phenotype can alter its recognition of potentially cytotoxic agents and its defense mechanisms against cell death. These observations support the view that beta-cells are not necessarily passive victims of a cytotoxic process but can actively participate in a process of beta-cell death. Their role will be influenced by neighboring non-beta-cells, which can make the islet internal milieu more protective or toxic for the beta-cells. We consider duct cells as potentially important contributors to this local process.

show abstract

Prevalence of Residual Beta-cell Function in Insulin-Dependent Diabetics in Relation to Age at Onset and Duration of Diabetes

Cited by 103 publications

References 0 publications

Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion

Postprandial Suppression of Glucagon Secretion Depends on Intact Pulsatile Insulin Secretion

Beta cell function during rapamycin monotherapy in long-term type 1 diabetes

Role of pancreatic beta-cells in the process of beta-cell death.

Contact Info

Product

Resources

About