β‐cell deterioration – prospects for reversal or prevention

Finegood, Diane T.; Topp, Brian

doi:10.1046/j.1463-1326.2001.00030.x

Cited by 23 publications

(18 citation statements)

References 90 publications

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“…Humans and animals with Type 2 diabetes display insulin resistance, insulin secretory defects and insufficient (possibly reduced) beta cell mass [16,17,18,19,20]. Several authors have suggested that diabetes is characterised by insufficient beta cell adaptation to insulin resistance [15,21,22] followed by beta cell failure.…”

Section: Discussionmentioning

confidence: 99%

Metabolic adaptations to chronic glucose infusion in rats

2004

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Aims/hypothesis. Several studies have employed the chronic glucose infusion protocol to quantify the metabolic adaptations associated with a prolonged glucose challenge. However, the limited number of indices and time points reported by these studies has generated an incomplete picture of this process. In this study we aimed to generate an integrative and dynamic picture of the physiological adaptations that occur during chronic glucose infusion. Methods. Sprague-Dawley rats were infused with either 50% dextrose or saline (2 ml/h) for a period of between 0 and 6 days. Glucose, insulin and NEFA dynamics were determined from daily blood samples. Subsets of animals were killed daily for histological determination of beta cell mass, size and replication rates. The mathematical model of coupled beta cell mass, insulin and glucose (the βIG model) was used to estimate insulin sensitivity, beta cell function and net neogenesis from this data. Results. Glucose-infused rats displayed transient hyperglycaemia, persistent hyperinsulinaemia and unchanged NEFA levels. Insulin sensitivity decreased by approximately 80% during the first day of glucose infusion, but had returned to pre-infusion levels by Day 3. Beta cell function was four to six times higher than in control rats throughout the experiment. Beta cell mass doubled over the 6 days of glucose infusion due to three phases of adaptation: (i) neogenesis; (ii) hypertrophy and hyperplasia; and (iii) continued hyperplasia coupled to a second wave of neogenesis. Conclusions/interpretation. Contrary to the results reported for perfused pancreas and in vitro experiments, we found that chronic glucose infusion elevated beta cell function. The prediction of a second wave of beta cell neogenesis, coupled with our previous report of "focal areas" on Day 3, suggests the existence of delayed acinar-to-islet transdifferentiation.

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Section: Discussionmentioning

confidence: 99%

Metabolic adaptations to chronic glucose infusion in rats

2004

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“…Lipotoxicity is also considered as a potential cause of β-cell population reduction. Thus, elevated lipogenesis prior to, or in association with hyperglycemia results in excessive accumulation of fatty acid into the β-cell cytoplasm [127]. ZDF rats are frequently used in comparative studies with non-diabetic fatty rats and lean ZDF.…”

Section: Tsumura Suzuki Obese Diabetic (Tsod) Mousementioning

confidence: 99%

Development of Improved Animal Models for the Study of Diabetes

Ciobotaru¹

2013

Diabetes Mellitus - Insights and Perspectives

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“…A potential role for IAPP in the development of insulin resistance, β -cell dysfunction, and T2DM has been proposed [ 35• ]. Some investigators have concluded that up to 90% of patients with T2DM have amyloid deposits in their islets [ 36 ] and the degree of amyloidosis correlates with disease duration and severity [ 37 ]. Human amyloid is toxic to β cells [ 38 ] and has been implicated in the loss of β -cell mass [ 39 ].…”

Section: Amyloidmentioning

confidence: 99%

β-cell failure in type 2 diabetes mellitus

Lencioni¹,

Lupi²,

Prato

2008

Curr Diab Rep

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Diabetes mellitus has been defined as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both" and encompasses a wide range of heterogeneous conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of genetic and acquired factors. However, lifestyle factors, particularly overeating and physical inactivity, are the major clinical determinants of T2DM. Insulin resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless progressive loss of beta-cell function develops. Significant reduction in beta-cell function is already present at the time of T2DM diagnosis, and it continuously declines irrespective of treatment. As such, the progressive loss of beta-cell function dictates the rate of worsened glycemic control. Development of progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta-cell function, and shrinkage of beta-cell mass. Understanding the causes for beta-cell failure is therefore of capital importance to develop new and more effective therapeutic strategies.

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β‐cell deterioration – prospects for reversal or prevention

Cited by 23 publications

References 90 publications

Metabolic adaptations to chronic glucose infusion in rats

Metabolic adaptations to chronic glucose infusion in rats

Development of Improved Animal Models for the Study of Diabetes

β-cell failure in type 2 diabetes mellitus

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