Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes

Diabetologia

Volumn 56, Issue 2, 2013, Pages 423-433

  Kang, Z F ^a,b   Deng, Y ^a   Zhou, Y ^a   Fan, R R ^a   Chan, J C N ^a,b   Laybutt, D R ^c   Luzuriaga, J ^c   Xu, G ^a,b  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

Dipeptidyl peptidase 4; Exendin 4; Glucagon like peptide 1; Glucose dependent insulinotropic polypeptide; Islet; NEFA; Non esterified fatty acid; Receptor

Indexed keywords

BEZAFIBRATE; CYCLIC AMP; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; EXENDIN 4; FATTY ACID; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSE; INCRETIN; MESSENGER RNA; PALMITIC ACID; SITAGLIPTIN; GLUCAGON RECEPTOR; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDIABETIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DOSE RESPONSE; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; GLUCAGON LIKE PEPTIDE 1 RECEPTOR GENE; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; IN VITRO STUDY; IN VIVO STUDY; INSULIN RELEASE; MALE; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; ANIMAL; C57BL MOUSE; DRUG EFFECT; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS;

ANIMALS; DIABETES MELLITUS, TYPE 2; FATTY ACIDS, NONESTERIFIED; INCRETINS; INSULIN-SECRETING CELLS; MALE; MICE; MICE, INBRED C57BL; RECEPTORS, GLUCAGON;

MLCS; MLOWN;

EID: 84878755846     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-012-2776-x     Document Type: Article

References (52)

1. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131-2157
2. Holst JJ, Vilsboll T, Deacon CF (2009) The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127-136
3. Nauck M, Stockmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46-52
4. Meier JJ, Nauck MA (2010) Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes 59:1117-1125
5. Nauck MA, Vardarli I, Deacon CF, Holst JJ, Meier JJ (2011) Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia 54:10-18
6. Lee S, Yabe D, Nohtomi K et al (2010) Intact glucagon-like peptide-1 levels are not decreased in Japanese patients with type 2 diabetes. Endocr J 57:119-126
7. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301-307
8. Kjems LL, Holst JJ, Volund A, Madsbad S (2003) The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 52:380-386
9. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ (2003) Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 278:471-478
10. Xu G, Stoffers DA, Habener JF, Bonner-Weir S (1999) Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270-2276
11. Fan R, Li X, Gu X, Chan JC, Xu G (2010) Exendin-4 protects pancreatic beta cells from human islet amyloid polypeptide-induced cell damage: potential involvement of AKT and mitochondria biogenesis. Diabetes Obes Metab 12:815-824
12. Nauck MA, Heimesaat MM, Behle K et al (2002) Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 87:1239-1246
13. Hare KJ, Vilsboll T, Asmar M, Deacon CF, Knop FK, Holst JJ (2010) The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action. Diabetes 59:1765-1770
14. Turton MD, O'Shea D, Gunn I et al (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379:69-72
15. Lovshin JA, Drucker DJ (2009) Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 5:262-269
16. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102-110
17. Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E (1995) A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38:1213-1217
18. McGarry JD, Dobbins RL (1999) Fatty acids, lipotoxicity and insulin secretion. Diabetologia 42:128-138
19. Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789
20. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH (1994) Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Proc Natl Acad Sci U S A 91:10878-10882
21. Crespin SR, Greenough WB 3rd, Steinberg D (1973) Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect. J Clin Invest 52:1979-1984
22. Zhou YP, Grill VE (1994) Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93:870-876
23. Kozawa J, Okita K, Imagawa A et al (2010) Similar incretin secretion in obese and non-obese Japanese subjects with type 2 diabetes. Biochem Biophys Res Commun 393:410-413
24. Muscelli E, Mari A, Casolaro A et al (2008) Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57:1340-1348
25. Knop FK, Aaboe K, Vilsbøll T et al (2012) Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab 14:500-510
26. Bando Y, Aoki H, Hisada K, Toya A, Tanaka D (2012) Obesity may attenuate the HbA1c-lowering effect of sitagliptin in Japanese type 2 diabetic patients. J Diabetes Investig 3:170-174
27. Xu G, Kaneto H, Laybutt DR et al (2007) Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes 56:1551-1558
28. Hojberg PV, Vilsboll T, Rabol R et al (2009) Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52:199-207
29. Laybutt DR, Preston AM, Akerfeldt MC et al (2007) Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia 50:752-763
30. Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CH, Maedler K (2009) Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 18:2388-2399
31. Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29:351-366
32. Kjorholt C, Akerfeldt MC, Biden TJ, Laybutt DR (2005) Chronic hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of beta-cell differentiation and secretory function in the db/db mouse model of diabetes. Diabetes 54:2755-2763
33. Jhala US, Canettieri G, Screaton RA et al (2003) cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev 17:1575-1580
34. Lamont BJ, Li Y, Kwan E, Brown TJ, Gaisano H, Drucker DJ (2012) Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice. J Clin Invest 122:388-402
35. Piteau S, Olver A, Kim SJ et al (2007) Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat. Biochem Biophys Res Commun 362:1007-1012
36. Kato T, Shimano H, Yamamoto T et al (2008) Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. Diabetes 57:2382-2392
37. Young AA, Gedulin BR, Bhavsar S et al (1999) Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 48:1026-1034
38. Lamont BJ, Drucker DJ (2008) Differential antidiabetic efficacy of incretin agonists versus DPP-4 inhibition in high fat fed mice. Diabetes 57:190-198
39. Mu J, Woods J, Zhou YP et al (2006) Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes. Diabetes 55:1695-1704
40. Wang Q, Brubaker PL (2002) Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 45:1263-1273
41. Rolin B, Larsen MO, Gotfredsen CF et al (2002) The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice. Am J Physiol Endocrinol Metab 283:E745-E752
42. Fan R, Kang ZF, He L, Chan JC, Xu G (2011) Exendin-4 improves blood glucose control in both young and aging normal non-diabetic mice, possible contribution of beta cell independent effects. PLoS One 6:e20443
43. Sathananthan A, Man CD, Micheletto F et al (2010) Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study. Diabetes Care 33:2074-2076
44. Saxena R, Hivert MF, Langenberg C et al (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142-148
45. Bolen S, Feldman L, Vassy J et al (2007) Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 147:386-399
46. Maida A, Hansotia T, Longuet C, Seino Y, Drucker DJ (2009) Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for beta cell survival in mice. Gastroenterology 137:2146-2157
47. Nie Y, Ma R, Chan JC, Xu H, Xu G (2012) Glucose-dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose-dependent insulinotropic peptide receptor over-expressing adipocytes. FASEB J 26:2383-2393
48. Lynn FC, Thompson SA, Pospisilik JA et al (2003) A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. FASEB J 17:91-93
49. Ravnskjaer K, Boergesen M, Rubi B et al (2005) Peroxisome proliferator-activated receptor alpha (PPARalpha) potentiates, whereas PPARgamma attenuates, glucose-stimulated insulin secretion in pancreatic beta-cells. Endocrinology 146:3266-3276
50. Lalloyer F, Vandewalle B, Percevault F et al (2006) Peroxisome proliferator-activated receptor alpha improves pancreatic adaptation to insulin resistance in obese mice and reduces lipotoxicity in human islets. Diabetes 55:1605-1613
51. Maida A, Lamont BJ, Cao X, Drucker DJ (2011) Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-alpha in mice. Diabetologia 54:339-349
52. Gupta D, Peshavaria M, Monga N, Jetton TL, Leahy JL (2010) Physiologic and pharmacologic modulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta-cells by peroxisome proliferator-activated receptor (PPAR)-gamma signaling: possible mechanism for the GIP resistance in type 2 diabetes. Diabetes 59:1445-1450