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. 2013 Aug;36 Suppl 2(Suppl 2):S113-9.
doi: 10.2337/dcS13-2008.

Role of reduced β-cell mass versus impaired β-cell function in the pathogenesis of type 2 diabetes

Juris J Meier  1 , Riccardo C Bonadonna
Affiliations

Role of reduced β-cell mass versus impaired β-cell function in the pathogenesis of type 2 diabetes

Juris J Meier et al. Diabetes Care. 2013 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Working model for the impact of reduced β-cell mass on the pathogenesis of type 2 diabetes. In patients with type 2 diabetes, β-cell mass is reduced by ∼20–65%, leading to impaired and delayed insulin secretion and a specific reduction in the amplitude of pulsatile insulin secretion. The reduction of insulin secretion and insulin pulsatility leads to disruption of the intraislet insulin-glucagon cross-talk, causing insufficient suppression of glucagon release. Reduced pulsatile insulin secretion impairs hepatic insulin signaling and perturbs peripheral insulin action. Increased hepatic glucose release is further augmented by the exaggerated glucagon concentrations. Together, these defects cause hyperglycemia in patients with type 2 diabetes.
Figure 2
Figure 2
Stimulus response curve for first-phase (derivative control of β-cell function) (continuous lines) and second-phase (proportional control of β-cell function) (dotted lines) insulin release in control subjects (C) and in patients with type 2 diabetes (T2DM). All subjects underwent a number of hyperglycemic clamps at graded glucose levels to construct a stimulus response curve in each. Although both first- and second-phase insulin releases are severely impaired in the patients (P < 0.01 for both, type 2 diabetic vs. control), second phase shows a graded response to the glucose challenge, whereas first phase is virtually absent in the patients, thereby showing asymmetric functional defects. Data are redrawn from ref. .
Figure 3
Figure 3
Relationship between pancreatic β-cell area, as determined from pancreatic tissue removed at surgery, and the C-peptide–to–glucose ratio determined in the fasting state (A) and 30 min after oral glucose ingestion in 8 individuals with normal glucose tolerance (NGT), 14 with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 11 with diabetes. r and P values were calculated by linear regression analysis. These analyses demonstrate the tight relationship between β-cell mass and β-cell function. Modified from ref. .
Figure 4
Figure 4
Consensus model for the relationship between impaired β-cell function and mass in type 2 diabetes. A reduction in β-cell mass increases the secretory demand to the remaining β-cells, thereby disturbing β-cell function. This may lead to hyperglycemia and hyperlipidemia, which may again induce β-cell apoptosis, thereby aggravating the β-cell deficit. Along the same lines, the vicious circle may be initiated by a primary defect in β-cell function. The detrimental effects of hyperglycemia and β-cell exhaustion on β-cell mass and function may involve both oxidative stress and ER stress. FFA, free fatty acid.
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References

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