HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 56:M575-M579 (2001)
© 2001 The Gerontological Society of America

Effect of Aging and Diabetes on the Enteroinsular Axis

Judit Korosia, Christopher H.S. McIntoshb, Raymond A. Pedersonb, Hans-Ulrich Demuthc, Joel F. Habenerd, Ronald Gingeriche, Josephine M. Eganf, Dariush Elahid and Graydon S. Meneillya

a Departments of Medicine, University of British Columbia, Vancouver, Canada
b Departments of Physiology, University of British Columbia, Vancouver, Canada
c Hans Kneoll Institute for Natural Product Research, Halle, Germany
d Department of Medicine, Harvard University, Boston, Massachusetts
e Linco Research Inc., St. Charles, Missouri
f Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland

Graydon S. Meneilly, Rm S 169, Vancouver Hospital and Health Sciences Centre, UBC Site 2211, Wesbrook Mall, Vancouver, BC V6T 2B5 E-mail: meneilly{at}interchange.ubc.ca.

Decision Editor: John E. Morley, MB, BCh


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. The current studies were designed to examine the effect of aging and diabetes on the enteroinsular axis.

Methods. Healthy young control subjects (n = 10 young; age 23 ± 1 years; body mass index [BMI] 24 ± 1 kg/m2), healthy elderly subjects (n = 10; age 80 ± 2 years; BMI 26 ± 1 kg/m2), and elderly patients with type 2 diabetes (n = 10; age 76 ± 2 years; BMI 26 ± 2 kg/m2) underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m2).

Results. Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in elderly patients with diabetes and young controls than in elderly controls (young control: 178 ± 27 pM; elderly control: 355 ± 57 pM; elderly diabetes: 177 ± 30 pM; p < .05 elderly control vs young control and elderly diabetes). Total glucagon-like peptide 1 (GLP-1) responses were not significantly different between young and elderly controls and patients with diabetes (young control: 15 ± 2 pM; old control: 8 ± 2 pM; elderly diabetes: 12 ± 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 ± 1 pM; old control: 6 ± 1 pM; elderly diabetes: 7 ± 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 ± 2 pM; old control: 2 ± 2 pM; elderly diabetes: 4 ± 2 pM; p < .05, young vs elderly). Glucose-dependent insulinotropic polypeptide responses were not different between young and elderly controls and between elderly controls and patients with diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 ± 12 pM; elderly control: 121 ± 16 pM; elderly diabetes: 173 ± 27 pM; p < .05, young vs elderly diabetes). Glucagon responses were reduced in elderly controls but were similar in young controls and elderly patients with diabetes (young control: 15 ± 1 pM; elderly control: 9 ± 1 pM; elderly diabetes: 16 ± 1 pM; p < .01 elderly control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels were lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 ± 0.01; elderly control: 0.15 ± 0.01; elderly diabetes: 0.15 ± 0.01 {Delta}OD/20 minutes; p < .05, elderly vs young).

Conclusions. We conclude that normal aging and diabetes are associated with multiple changes in the enteroinsular axis.

THE term enteroinsular axis refers to the signaling pathways between the gut and pancreatic islets that enhance the insulin response to absorbed nutrients (1). Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are the most important insulin-releasing hormones (incretins) in this axis (1). The biologic effect of these peptides is partly regulated through metabolism by dipeptidyl peptidase IV (DPIV) (2), an enzyme that cleaves the first two amino acids from both GIP and GLP-1 (3)(4)(5).

Normal aging is characterized by a progressive increase in the prevalence of glucose tolerance and diabetes, so that by age 75 approximately 40% of the population has one of these metabolic abnormalities (6). In normal elderly subjects, glucose-induced insulin release from the pancreas is impaired, and this defect is accentuated in elderly patients with diabetes (7)(8)(9)(10). Previous studies have demonstrated that the responses of GIP and GLP-1 to oral glucose are both normal (11)(12)(13) or increased (14) in healthy elderly subjects when compared with healthy young controls. In elderly patients with diabetes, GIP responses to oral glucose are clearly enhanced (12). The response of the ß cell to both GIP and GLP-1 is impaired in normal elderly subjects and to a much greater extent in elderly patients with diabetes (7)(12)(14)(15). The mechanism for this effect is unclear, but one possibility for the reduced effectiveness of incretins in elderly persons is that these peptides are inactivated to a greater extent by DPIV.

There is increasing interest in the use of inhibitors of DPIV as treatments for glucose intolerance and diabetes because these agents would presumably increase the activity of incretin hormones, thereby reversing the defect in insulin secretion seen in these conditions (16). The objective of this study was to determine the effect of aging and diabetes on the incretin reponse to oral glucose and the changes in DPIV activity that occur in concert with these incretin responses.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Experimental Subjects
Subject characteristics are shown in Table 1 . Healthy controls had a normal history and physical examination, normal laboratory tests, normal kidney and liver function, and a normal electrocardiogram. All healthy controls had a normal glucose tolerance test by the National Diabetes Data Group Criteria. Patients with diabetes were recruited from the Vancouver Hospital Diabetes Centre. The mean duration of diabetes was 7 ± 1 years, and Hgb A1C was 8.0 ± 0.4%. All subjects were free of clinically significant microvascular, macrovascular, or neuropathic complications from their diabetes. Patients with hypertension were not excluded. Five of the elderly subjects were treated with sulfonylurea drugs, and five were being treated with angiotensin-converting enzyme inhibitors for hypertension. All medications were stopped at least 2 weeks prior to the test. This study was approved by the committee on Human Investigation at the University of British Columbia. All subjects gave written, informed consent prior to participation.


View this table:
[in this window]
[in a new window]
  		Table 1. Subject Characteristics

 
Experimental Protocol
All subjects underwent an oral glucose tolerance test. Subjects consumed a diet containing at least 200 g carbohydrate for 3 days prior to each test and were studied after a 12-hour overnight fast. Blood samples were taken at -10 and 0 minutes. Subjects were then given glucose (40 g/m2), and blood samples were taken every 30 minutes to 180 minutes. Plasma glucose was measured immediately at the bedside using a YSI Glucose Analyzer (Yellowsprings Instruments, Yellowsprings, OH). Samples for DPIV were collected in heparin only. The remaining blood was placed in pre-chilled test tubes containing isoleucine thiazolidine (for measurement of GIP and GLP-1) (17), aprotonin (400 KIU/ml) and ethylenediaminetetraacetic acid (1.5 mg/ml) (for measurement of glucagon) and centrifuged at 4°C. Samples were stored at –70°C until analysis. Insulin, glucagon, and GIP were measured by radioimmunoassays as previously described (15). Total GLP-1 antibody is directed at the C-terminal end of the molecule and thus recognizes the intact forms of GLP-1 as well as the truncated forms. Active GLP-1was measured in the assay services department at Linco Research Inc. using an ELISA technique. This assay measures both the 7-36 and the 7-37 GLP-1 moieties and excludes completely the 9-36 and 9-37 truncated forms. Plasma DPIV activity was measured by a colorimetric assay as previously described (4)(18).

Data are presented as mean ± standard error of the mean. The area under the curve was calculated according to the Trapezoidal Rule. All values in the results for insulin, glucose, glucagon, GLP-1, and GIP are presented as the AUC. Differences between groups were determined using analysis of variance followed by Bonferroni's correction for pairwise comparisons. A p value of .05 was considered significant in all analyses.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Elderly controls and patients with diabetes were similar in body mass index. Young control subjects appeared to have a lower BMI than elderly subjects, but the difference did not reach statistical significance.

Glucose, insulin, and glucagon values during the oral glucose tolerance test are shown in Fig. 1. As expected, the AUC for glucose values was higher in patients with diabetes than in both young and elderly controls (p < .0001), but there was no significant difference between young and elderly controls. Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in young controls and elderly patients with diabetes than in elderly controls (young control: 178 ± 27 pM; elderly control: 355 ± 57 pM; elderly diabetes: 177 ± 30 pM; p < .05, elderly control vs young control and elderly diabetes). Glucagon values were greater in elderly patients with diabetes and young controls when compared with elderly controls (young control: 15 ± 1 pM; elderly control: 9 ± 1 pM; elderly diabetes: 16 ± 1 pM; p < .01, elderly control vs young control and elderly diabetes).



View larger version (21K):
[in this window]
[in a new window]
  		Figure 1. Glucose, insulin values, and glucagon values during the oral glucose tolerance test.

 
GLP-1 values are shown in Fig. 2. Total GLP-1 responses were not significantly different between young and elderly controls and patients with diabetes (young control: 15 ± 2 pM; old control: 8 ± 2 pM; elderly diabetes: 12 ± 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 ± 1 pM; old control: 6 ± 1 pM; elderly diabetes: 7 ± 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 ± 2 pM; old control: 2 ± 2 pM; elderly diabetes: 4 ± 2 pM; p < .05, young control vs elderly control and elderly diabetes). GIP and DPIV responses are shown in Fig. 3. GIP responses were not different between young and elderly controls and between elderly controls and patients with diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 ± 12 pM; elderly control: 121 ± 16 pM; elderly diabetes: 173 ± 27 pM; p < .05, young control vs elderly diabetes). The AUC for DPIV activity was lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 ± 0.01; elderly control: 0.15 ± 0.01; elderly diabetes: 0.15 ± 0.01 {Delta}OD/20 minutes; p < .05, both elderly groups vs young).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 2. Total and active glucagon-like peptide 1 (GLP-1) levels during the oral glucose tolerance test.

 


View larger version (21K):
[in this window]
[in a new window]
  		Figure 3. Glucose-dependent insulinotropic polypeptide (GIP) and dipeptidyl peptidase IV (DPIV) levels during the oral glucose tolerance test.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
In this study, we examined multiple components of the enteroinsular axis in healthy young and old and elderly patients with diabetes. Insulin responses to the oral glucose challenge appeared to be greater in the healthy elderly subjects than in the healthy young subjects; however, this may have been a result of the higher glucose levels in elderly persons, and we believe that our results are consistent with previous studies that have demonstrated subtle alterations in glucose-induced insulin release in healthy elderly individuals (7)(8). Similar to our previous results, we demonstrated a profound impairment in glucose-induced insulin release in relatively lean elderly patients with diabetes when compared with age- and weight-matched controls (9)(10). Few studies have evaluated the changes with age in glucagon physiology. Fasting glucagon levels have been reported to be normal in elderly persons and to suppress normally in response to intravenous glucose and insulin (11)(19)(20)(21). However, suppression of glucagon levels in response to oral glucose has been found to be impaired in healthy elderly subjects (11). We and others have documented that the glucagon responses to hypoglycemia are impaired with aging (22)(23)(24). In this study we found that glucagon levels were reduced in elderly controls, but glucagon reponses to oral glucose were similar in elderly patients with diabetes and young controls. We demonstrate for the first time that, similar to middle-aged patients with diabetes, glucagon levels are elevated in elderly patients with diabetes relative to controls.

Few studies have evaluated the changes in the physiology of GLP-1 with age. Ranganath and colleagues reported substantial increases in GLP-1 responses to oral glucose in healthy elderly women when compared with young controls (14). In contrast, MacIntosh and colleagues (13) found that the GLP-1 responses to oral glucose were similar in healthy young and old men. In a mixed group of men and women, we could find no differences between young subjects and either normal elderly subjects or elderly patients with diabetes in the total GLP-1 responses to oral glucose. In this study, we report for the first time active GLP-1 values in elderly controls and patients with diabetes and found no difference in these values between groups. However, we found that the difference between total and active GLP-1 was lower in elderly controls and patients with diabetes, suggesting reduced inactivation of this peptide with age (see below). Despite preserved levels of active GLP-1 in these patients, glucose-induced insulin release was markedly impaired, consistent with a reduction in ß-cell sensitivity to GLP-1 in elderly patients with diabetes.

Previous reports suggested that GIP responses to oral glucose are either normal (11)(12)(13) or increased (14) in healthy elderly subjects when compared with young controls. In this study and other previous studies that did not find an age-related increase in GIP responses to oral glucose (11)(12)(13), there was a trend, which did not reach statistical significance, toward increased GIP levels in healthy elderly subjects.. We suspect that the lack of a significant effect in our study and other previous reports is due to a type 2 error and that overall there is a modest increase in GIP responses in healthy elderly subjects. Further support for this hypothesis is that normal aging is characterized by subtle alterations in glucose-induced insulin secretion (7)(8) and the ß-cell response to GIP is reduced with age (7)(12). In the presence of a normal feedback mechanism between GIP and insulin secretion, this would serve to modestly enhance GIP secretion. We confirm our previous findings that GIP responses to oral glucose are markedly enhanced in elderly patients with diabetes and that the ß-cell response to GIP is impaired (12)(15)(25). This is not surprising in view of the profound impairment in glucose-induced secretion in these patients (9)(10)(26) and suggests a normal feedback relationship in the enteroinsular axis in these patients in regard to GIP. We believe that the increased levels of GIP we find in elderly patients with diabetes are due to increased secretion of the peptide. The radioimmunoassay used to measure GIP measures both active and inactive forms of the peptide (27). It is possible that the increased levels of GIP we found were purely a result of decreased degradation of the peptide by DPIV. We think this is unlikely because this would have resulted in an equivalent elevation of GIP in both normal elderly and diabetic subjects. Further characterization of circulating GIP measured with assays that separate the active and inactive peptide will need to be performed before definitive conclusions can be made.

In this study, we demonstrate that, contrary to our initial hypothesis, DPIV activity was reduced in both elderly controls and patients with diabetes. It is possible that the body has adapted to reduced glucose-induced insulin secretion by decreasing the activity of DPIV, which would result in reduced degradation of incretins. This would result in increased active levels of these peptides and enhance glucose-induced insulin secretion. The DPIV enzyme is produced in multiple tissues and has been found in plasma in many different forms (28)(29)(30)(31). Circulating DPIV activity therefore appears to consist of a mixture of different proline dipeptidases (32). There are several potential mechanisms whereby the activity of the peptide could be reduced, including decreased biosynthesis, reduced release into plasma, or increased breakdown and clearance of the circulating form. Intuitively, we would have expected a greater reduction in DPIV activity in patients with diabetes to compensate for their marked impairment in insulin secretion. Further studies that characterize the form of DPIV specific to the catabolism of incretins will be needed to resolve this issue.

DPIV inhibitors are being investigated as therapeutic interventions in middle-aged patients with type 2 diabetes (16). Our current findings suggest that these interventions may be less effective in elderly patients due to reduced activity of DPIV. To enhance the effectiveness of incretins, it will be necessary not only to inhibit degradation but to increase secretion and enhance activity at the cellular level. Further studies are clearly needed to determine the effectiveness of DPIV inhibitors and other manipulations of the enteroinsular axis on insulin secretion in elderly patients.


   Acknowledgments
 
This study was supported by a grant from the Canadian Diabetes Association (in honor of Irene Brookes) and by a grant from the Medical Research Council of Canada. We gratefully acknowledge the support of the Alan McGavin Geriatric Medicine Endowment of the University of British Columbia and the Jack Bell Geriatric Endowment Fund at Vancouver General Hospital.

We are grateful to Kathryn Galt for assistance in the preparation of the manuscript and to Christine Lockhart, Gail Chin, Norman Hodges, and Rosemary Torressani for technical assistance.

Received September 7, 2000

Accepted September 14, 2000


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Habener JF, 1993. The incretin concept and its relevance to diabetes. Endocrinol Metab Clin North Am. 22:775-794. [Medline]
  2. Demuth H-U, Heins J, 1995. Catalytic mechanism of dipeptidyl peptidase IV. Fleischer B, , ed.Dipeptidyl Peptidase IV (CD 26) in Metabolism and the Immune Response 1-37. R.G. Landes Biochemical Publishers, Georgetown, SC.
  3. Mentlein R, Gallwitz B, Schmidt WE, 1993. Dipeptidyl-peptidase IV hydrolyzes gastric inhibitory polypeptide, glucagon-like-peptide-1 (7–36), and peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 214:829-835. [Medline]
  4. Kieffer TJ, McIntosh CHS, Pederson RA, 1995. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like-peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136:3585-3596. [Abstract]
  5. Pauly RP, Rosche F, Wermann M, McIntosh CHS, Pederson RA, Demuth H-U, 1996. Investigation of glucose-dependent insulinotropic polypeptide (1–42) and glucagon-like peptide-1 (70–36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ionization time of flight mass spectrometry. J Biol Chem. 271:23222-23229. [Abstract/Free Full Text]
  6. Harris MI, Flegal KM, Cowie CC, et al. 1998. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. Diabetes Care. 21:518-526. [Abstract]
  7. Meneilly GS, Ryan AS, Minaker KL, Elahi D, 1998. The effect of age and glycemic level on the response of the ß-cell to glucose-dependent insulinotropic polypeptide and peripheral tissue sensitivity to endogenously released insulin. J Clin Endocrinol Metab. 83:2925-2932. [Abstract/Free Full Text]
  8. Meneilly GS, Ryan AS, Veldhuis JD, Elahi D, 1997. Increased disorderliness of basal insulin release, attenuated insulin secretory burst mass, and reduced ultradian rhythmicity of insulin secretion in older individuals. J Clin Endocrinol Metab. 82:4088-4093. [Abstract/Free Full Text]
  9. Meneilly GS, Elliott T, Tessier D, Hards L, Tildesly H, 1996. NIDDM in the elderly. Diabetes Care. 19:1320-1325. [Abstract]
  10. Meneilly GS, Elliott T, 1999. Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. Diabetes Care. 22:112-118. [Abstract/Free Full Text]
  11. McConnell JG, Alam MJ, O'Hare MMY, Buchanan KD, Stout RW, 1983. The effect of age and sex on the response of enteropancreatic polypeptides to oral glucose. Age Ageing. 12:54-62. [Abstract/Free Full Text]
  12. Elahi D, Andersen DK, Muller DC, Tobin JD, Brown JC, Andres R, 1984. The enteric enhancement of glucose-stimulated insulin release: the role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus. Diabetes. 33:950-957. [Abstract]
  13. MacIntosh CG, Andrews JM, Jones KL, et al. 1999. Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am J Clin Nutr. 69:999-1006. [Abstract/Free Full Text]
  14. Ranganath L, Sedgwick I, Morgan L, Wright J, Marks V, 1998. The aging entero-insular axis. Diabetologia. 41:1309-1313. [Medline]
  15. Elahi D, McAloon-Dyke M, Fukagawa NK, et al. 1994. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7–37) in normal and diabetic subjects. Regul Pept. 51:63-74. [Medline]
  16. Holst JJ, Deacon CF, 1998. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 47:1663-1670. [Abstract]
  17. Pederson RA, White HA, Schlenzig D, Pauly RP, McIntosh CHS, Demuth H-U, 1998. Improved glucose tolerance in Zucker fatty rats by oral administration of the Dipeptidyl Peptidase IV inhibitor isoleucine thiazolidide. Diabetes. 47:1253-1258. [Abstract]
  18. Pederson RA, Kieffer TJ, Pauly R, Kofod H, Kwong J, McIntosh CHS, 1996. The enteroinsular axis in dipeptidyl peptidase IV-negative rats. Metabolism. 45:1336-1341.
  19. Simonson DC, DeFronzo RA, 1983. Glucagon physiology and aging: evidence for enhanced hepatic sensitivity. Diabetologia. 25:1-7. [Medline]
  20. Dudl RJ, Ensinck JW, 1977. Insulin and glucagon relationships during aging in man. Metabolism 26:33-41. [Medline]
  21. Berger D, Crowther R, Floyd JC, Pek S, Fajans SS, 1988. Effects of age on fasting levels of pancreatic hormones in man. J Clin Endocrinol Metab. 47:1183-1189. [Abstract/Free Full Text]
  22. Marker JC, Cryer PE, Clutter WE, 1992. Attenuated glucose recovery from hypoglycemia in the elderly. Diabetes 41:671-678. [Abstract]
  23. Meneilly GS, Cheung E, Tuokko H, 1994. Altered responses to hypoglycemia of healthy elderly people. J Clin Endocrinol Metab. 78:1341-1348. [Abstract]
  24. Meneilly GS, Cheung E, Tuokko H, 1994. Counterregulatory hormone responses to hypoglycemia in the elderly patient with diabetes. Diabetes. 43:403-410. [Abstract]
  25. Meneilly GS, Bryer-Ash M, Elahi D, 1993. The effect of glyburide on beta-cell sensitivity to glucose-dependent insulinotropic polypeptide. Diabetes Care. 16:110-114. [Abstract]
  26. Arner P, Pollare T, Lithell H, 1991. Different aetiologies of type 2 diabetes mellitus in obese and non-obese subjects. Diabetologia. 34:483-487. [Medline]
  27. Krarup T, 1988. Immunoreactive gastric inhibitory polypeptide. Endocr Rev. 9:122-134. [Abstract/Free Full Text]
  28. Duke-Cohan JS, Morimoto C, Rocker JA, Schlossman SF, 1995. A novel form of dipeptidylpeptidase IV found in human serum: isolation, characterization, and comparison with T lymphocyte membrane dipepti-dylpeptidase IV (CD26). J Biol Chem. 270:14107-14114. [Abstract/Free Full Text]
  29. Iwaki-Egawa S, Watanabe Y, Kikuya Y, Fujimoto Y, 1998. Dipeptidyl peptidase IV from human serum: purification, characterization, and N-ter-minal amino acid sequence. J Biochem. 124:428-433. [Abstract/Free Full Text]
  30. Shibuya-Saruta H, Kasahara Y, Hashimoto Y, 1996. Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties. J Clin Lab Anal. 10:435-440. [Medline]
  31. Duke-Cohan JS, Morimoto C, Rocker JA, Schlossman SF, 1996. Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells. J Immunol. 156:1714-1721. [Abstract]
  32. Blanco J, Nguyen C, Callebaut C, et al. 1998. Dipeptidyl-peptidase IV-ß: further characterization and comparison to dipeptidyl-peptidase IV activity of CD26. Eur J Biochem. 256:369-378. [Medline]



This article has been cited by other articles:


Home page
 Diabetes CareHome page
R. E. Pratley, J. Rosenstock, F. X. Pi-Sunyer, M. A. Banerji, A. Schweizer, A. Couturier, and S. Dejager
Management of Type 2 Diabetes in Treatment-Naive Elderly Patients: Benefits and risks of vildagliptin monotherapy
Diabetes Care, December 1, 2007; 30(12): 3017 - 3022.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
D. O'Donovan, C. Feinle-Bisset, C. Chong, A. Cameron, A. Tonkin, J. Wishart, M. Horowitz, and K. L. Jones
Intraduodenal Guar Attenuates the Fall in Blood Pressure Induced by Glucose in Healthy Older Adults
J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 940 - 946.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. M. Chang and J. B. Halter
Aging and insulin secretion
Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E7 - E12.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
G. S. Meneilly, C. H.S. McIntosh, R. A. Pederson, J. F. Habener, R. Gingerich, J. M. Egan, and D. Elahi
Glucagon-like Peptide-1 (7-37) Augments Insulin-Mediated Glucose Uptake in Elderly Patients With Diabetes
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2001; 56(11): M681 - 685.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS