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Published in: Diabetologia 1/2010

Open Access 01-01-2010 | Article

Relationship between fractional pancreatic beta cell area and fasting plasma glucose concentration in monkeys

Authors: Y. Saisho, A. E. Butler, E. Manesso, R. Galasso, L. Zhang, T. Gurlo, G. M. Toffolo, C. Cobelli, K. Kavanagh, J. D. Wagner, P. C. Butler

Published in: Diabetologia | Issue 1/2010

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Abstract

Aims/hypothesis

We sought to establish the relationship between fasting plasma glucose concentrations and pancreatic fractional beta cell area in adult cynomolgus monkeys (Macaca fascicularis).

Methods

Fasting plasma glucose and pancreatic fractional beta cell area were measured in 18 control and 17 streptozotocin-treated adult primates (17.0 ± 1.2 vs 15.4 ± 1.2 years old).

Results

Fasting plasma glucose was increased (12.0 ± 2.0 vs 3.4 ± 0.1 mmol/l, p < 0.01) and fractional beta cell area was decreased (0.62 ± 0.13% vs 2.49 ± 0.35%, p < 0.01) in streptozotocin-treated monkeys. The relationship between fasting plasma glucose and pancreatic fractional beta cell area was described by a wide range of beta cell areas in controls. In streptozotocin-treated monkeys there was an inflection of fasting blood glucose at ∼50% of the mean beta cell area in controls with a steep increase in blood glucose for each further decrement in beta cell area.

Conclusions/interpretation

In adult non-human primates a decrement in fractional beta cell area of ∼50% or more leads to loss of glycaemic control.
Literature
1.
go back to reference Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331CrossRefPubMed Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331CrossRefPubMed
2.
go back to reference 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 52:102–110CrossRefPubMed 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 52:102–110CrossRefPubMed
3.
go back to reference Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC (2006) Relationship between beta-cell mass and fasting blood glucose concentration in humans. Diabetes Care 29:717–718CrossRefPubMed Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC (2006) Relationship between beta-cell mass and fasting blood glucose concentration in humans. Diabetes Care 29:717–718CrossRefPubMed
4.
go back to reference King J, Kazanjian K, Matsumoto J et al (2008) Distal pancreatectomy: incidence of postoperative diabetes. J Gastrointest Surg 12:1548–1553CrossRefPubMed King J, Kazanjian K, Matsumoto J et al (2008) Distal pancreatectomy: incidence of postoperative diabetes. J Gastrointest Surg 12:1548–1553CrossRefPubMed
5.
go back to reference Lillemoe KD, Kaushal S, Cameron JL, Sohn TA, Pitt HA, Yeo CJ (1999) Distal pancreatectomy: indications and outcomes in 235 patients. Ann Surg 229:693–698 discussion 698–700CrossRefPubMed Lillemoe KD, Kaushal S, Cameron JL, Sohn TA, Pitt HA, Yeo CJ (1999) Distal pancreatectomy: indications and outcomes in 235 patients. Ann Surg 229:693–698 discussion 698–700CrossRefPubMed
6.
go back to reference Matveyenko AV, Veldhuis JD, Butler PC (2006) Mechanisms of impaired fasting glucose and glucose intolerance induced by an approximate 50% pancreatectomy. Diabetes 55:2347–2356CrossRefPubMed Matveyenko AV, Veldhuis JD, Butler PC (2006) Mechanisms of impaired fasting glucose and glucose intolerance induced by an approximate 50% pancreatectomy. Diabetes 55:2347–2356CrossRefPubMed
7.
go back to reference Robertson RP, Lanz KJ, Sutherland DE, Seaquist ER (2002) Relationship between diabetes and obesity 9 to 18 years after hemipancreatectomy and transplantation in donors and recipients. Transplantation 73:736–741CrossRefPubMed Robertson RP, Lanz KJ, Sutherland DE, Seaquist ER (2002) Relationship between diabetes and obesity 9 to 18 years after hemipancreatectomy and transplantation in donors and recipients. Transplantation 73:736–741CrossRefPubMed
8.
go back to reference Kumar AF, Gruessner RW, Seaquist ER (2008) Risk of glucose intolerance and diabetes in hemipancreatectomized donors selected for normal preoperative glucose metabolism. Diabetes Care 31:1639–1643CrossRefPubMed Kumar AF, Gruessner RW, Seaquist ER (2008) Risk of glucose intolerance and diabetes in hemipancreatectomized donors selected for normal preoperative glucose metabolism. Diabetes Care 31:1639–1643CrossRefPubMed
9.
go back to reference Ward WK, Wallum BJ, Beard JC, Taborsky GJ Jr, Porte D Jr (1988) Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs. Diabetes 37:723–729CrossRefPubMed Ward WK, Wallum BJ, Beard JC, Taborsky GJ Jr, Porte D Jr (1988) Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs. Diabetes 37:723–729CrossRefPubMed
10.
go back to reference Wagner JD, Zhang L, Greaves KA, Shadoan MK, Schwenke DC (2000) Soy protein reduces the arterial low-density lipoprotein (LDL) concentration and delivery of LDL cholesterol to the arteries of diabetic and nondiabetic male cynomolgus monkeys. Metabolism 49:1188–1196CrossRefPubMed Wagner JD, Zhang L, Greaves KA, Shadoan MK, Schwenke DC (2000) Soy protein reduces the arterial low-density lipoprotein (LDL) concentration and delivery of LDL cholesterol to the arteries of diabetic and nondiabetic male cynomolgus monkeys. Metabolism 49:1188–1196CrossRefPubMed
11.
go back to reference Carson ER, Cobelli C, Finkelstein L (1983) The mathematical modeling of metabolic and endocrine systems. Wiley, New York Carson ER, Cobelli C, Finkelstein L (1983) The mathematical modeling of metabolic and endocrine systems. Wiley, New York
12.
go back to reference Barrett PH, Bell BM, Cobelli C et al (1998) SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism 47:484–492CrossRefPubMed Barrett PH, Bell BM, Cobelli C et al (1998) SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism 47:484–492CrossRefPubMed
13.
go back to reference Kjems LL, Kirby BM, Welsh EM et al (2001) Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 50:2001–2012CrossRefPubMed Kjems LL, Kirby BM, Welsh EM et al (2001) Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 50:2001–2012CrossRefPubMed
14.
go back to reference Matveyenko AV, Butler PC (2006) Beta-cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in type 2 diabetes. Diabetes 55:2106–2114CrossRefPubMed Matveyenko AV, Butler PC (2006) Beta-cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in type 2 diabetes. Diabetes 55:2106–2114CrossRefPubMed
15.
go back to reference Saisho Y, Butler AE, Meier JJ et al (2007) Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 20:933–942CrossRefPubMed Saisho Y, Butler AE, Meier JJ et al (2007) Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 20:933–942CrossRefPubMed
16.
go back to reference Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC (2008) Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 10(Suppl 4):32–42CrossRefPubMed Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC (2008) Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 10(Suppl 4):32–42CrossRefPubMed
17.
go back to reference Meier JJ, Butler AE, Galasso R, Butler PC (2006) Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care 29:1554–1559CrossRefPubMed Meier JJ, Butler AE, Galasso R, Butler PC (2006) Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care 29:1554–1559CrossRefPubMed
18.
go back to reference Saisho Y, Butler AE, Monchamp T et al (2007) Does beta cell mass adaptively increase in response to obesity in humans? Diabetes 56(Suppl 1):A48 Saisho Y, Butler AE, Monchamp T et al (2007) Does beta cell mass adaptively increase in response to obesity in humans? Diabetes 56(Suppl 1):A48
19.
go back to reference Schwitzgebel VM, Somm E, Klee P (2009) Modeling intrauterine growth retardation in rodents: impact on pancreas development and glucose homeostasis. Mol Cell Endocrinol 304:78–83CrossRefPubMed Schwitzgebel VM, Somm E, Klee P (2009) Modeling intrauterine growth retardation in rodents: impact on pancreas development and glucose homeostasis. Mol Cell Endocrinol 304:78–83CrossRefPubMed
20.
go back to reference Freathy RM, Bennett AJ, Ring SM et al (2009) Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes 58:1428–1433CrossRefPubMed Freathy RM, Bennett AJ, Ring SM et al (2009) Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes 58:1428–1433CrossRefPubMed
21.
go back to reference Meier JJ, Menge BA, Breuer TG et al (2009) Functional assessment of pancreatic beta-cell area in humans. Diabetes 58:1595–1603CrossRefPubMed Meier JJ, Menge BA, Breuer TG et al (2009) Functional assessment of pancreatic beta-cell area in humans. Diabetes 58:1595–1603CrossRefPubMed
22.
go back to reference Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690CrossRefPubMed Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690CrossRefPubMed
23.
go back to reference Matveyenko AV, Butler PC (2008) Relationship between beta-cell mass and diabetes onset. Diabetes Obes Metab 10(Suppl 4):23–31CrossRefPubMed Matveyenko AV, Butler PC (2008) Relationship between beta-cell mass and diabetes onset. Diabetes Obes Metab 10(Suppl 4):23–31CrossRefPubMed
24.
go back to reference Paolisso G, Scheen AJ, Giugliano D et al (1991) Pulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency. J Clin Endocrinol Metab 72:607–615CrossRefPubMed Paolisso G, Scheen AJ, Giugliano D et al (1991) Pulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency. J Clin Endocrinol Metab 72:607–615CrossRefPubMed
Metadata
Title
Relationship between fractional pancreatic beta cell area and fasting plasma glucose concentration in monkeys
Authors
Y. Saisho
A. E. Butler
E. Manesso
R. Galasso
L. Zhang
T. Gurlo
G. M. Toffolo
C. Cobelli
K. Kavanagh
J. D. Wagner
P. C. Butler
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2010
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1552-z

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