7. -Cell Adaptation to Chronic Insulin Resistance in Obesity Polonsky KS et al. J Clin Invest . 1988;81:442-448. 160 8 AM 12 PM 4 PM 8 PM 12 AM 4 AM Normal (acute) Obese (chronic) Clock time (hours) Glucose (mg/dL) Meals 150 140 130 120 110 100 90 80 Clock time (hours) Insulin ( U/mL) 160 Meals 8 AM 12 PM 4 PM 8 PM 12 AM 4 AM 140 130 100 80 60 40 20 0 Normal (acute) Obese (chronic)
8.
9. Normal Relationship Between Insulin Sensitivity and Response: The Disposition Index Bergman RN et al. Diabetes . 2002;51(suppl 1):S212-S220. Insulin sensitivity Insulin sensitivity x insulin response = constant Insulin response 6,000 4,000 2,000 0 0 1 2 3 4
10. -Cell Adaptation to Insulin Resistance: Cross-sectional Data Fasting insulin (pmol/L) Insulin sensitivity index (x10 -5 min -1 /pmol/L) r=-0.73; P <0.0001 Kahn SE et al. Diabetes . 1993;42:1663-1672. Males (n=55 ) Females (n=38) 0 50 100 150 200 250 300 0 5 10 15 20 25 50th
11. -Cell Adaptation to Insulin Resistance: Longitudinal Data in Normal Women Insulin sensitivity index ( mol/kg/min per pmol/L) 400 800 600 200 0 0 0.2 0.1 0.3 0.4 3rd trimester Nonpregnant postpartum Insulin secretion rate (pmol/min) Buchanan TA. J Clin Endocrinol Metab . 2001;86:989-993. 1,000
12. Regulation of -Cell Mass: A Dynamic Process Increased -cell mass Decreased -cell mass -Cell mass Replication Apoptosis Neogenesis Hypertrophy Necrosis
13. -Cell Mass in Lean and Obese People: Autopsy Studies -Cell volume (mL) 0 0.3 0.4 0.2 0.1 0.5 Obese Lean Kl ö ppel G et al. Surv Synth Pathol Res . 1985;4:110-125. Obese Lean 0 1.0 2.0 3.0 4.0 -Cell volume (%) Butler AE et al. Diabetes. 2003;52:102-110.
14.
15. Plasticity of Islets: Experimental Increase in -Cell Mass in Response to IR Lingohr MK et al. Trends in Mol Med . 2002;8:375-384. Experimental overfeeding results in increased -cell numbers (hyperplasia) and increased -cell size (hypertrophy) SC=standard chow HF=high-fat (diet) SC HF H and E Insulin Glucagon/somatostatin Islet area -Cell size -/ -Cell size
16. Effect of High-Fat Diet on Islet Size and -Cell Hypertrophy Lingohr MK et al. Trends in Mol Med . 2002;8:375-384. SC=standard chow HF=high-fat (diet) * P <0.001 3 2 1 0 SC HF SC HF SC HF 200 100 0 0 200 100 47.5% 34.4% Islet area (% total pancreatic area) -Cell diameter ( M) -/ -Cell diameter ( M) * *
17. Neogenesis May Contribute to Increased Islet Mass in Obese Humans Section of pancreas stained for insulin Butler AE et al. Diabetes . 2003;52:102-110.
Notas do Editor
Normal Biology of Pancreatic -Cells and Insulin Secretion Familiarity with the normal biology of pancreatic -cells and the regulation of insulin secretion outlined in this section leads to a better understanding and appreciation of the pathophysiology of type 2 diabetes.
