GLP-1 blood sugar regulation in islet transplants • AIDSPIT 1994 • @1MEMO 20251114

Poster 13th Workshop of the AIDSPIT Study Group , Igls (Austria) January 23–25, 1994• Digitally remastered by author, publisher, M.P.M. van der Burg • Miracles•Media • 20251114 • TakeNode 810cc881-d084-4d2e-b252-d432918b1946 • #GLP1

GLP-1 blood sugar regulation in islet transplants

GLP-1 (glucagon-like peptide-1) is now well-known from the anti-diabetic drugs that mimic the action of this natural hormone GLP-1, to treat type 2 diabetes and obesity. They work by stimulating insulin release, reducing glucagon secretion, slowing stomach emptying, and suppressing appetite, which leads to lower blood sugar and weight loss.

May 1992 we were the first to show direct potentiation of the insulin response from isolated islets by a (near-)physiological dose of the gut hormone GLP-1 during perifusion (in vitro) of canine islets at 7.5-10 mM glucose levels (1,2).

Jan 1994 we next showed this incretin effect of GLP-1 also after islet transplantation (in vivo, in dogs) in this poster (3) and abstract (4) presented at the 13th Workshop of the AIDSPIT (aka AIDPIT) Study Group , Igls, Austria, January 23–25, 1994.

Background of the work was posted earlier this year (5) and the work was published Nov 1994 in my PhD thesis Pancreatic islet transplantation , available online (6).

Notes

1) Van der Burg MPM, Guicherit OR, Scherft JP, Frölich M, Terpstra JL, Gooszen HG. Function after intrasplenic transplantation of islets of Langerhans in dogs (translated from dutch: Functie na intralienale transplantatie van eilandjes van Langerhans in de hond). Surgeon days ’92 of the Dutch Surgery Society, Rotterdam (The Netherlands) May 21–22, 1992. In : Gut factors controlling pancreatic islets • 20240910 | Michel van der Burg | michelvanderburg•com URL https://michelvanderburg.com/2024/09/10/gut-factors-controlling-pancreatic-islets-20240910/

2) van der Burg MPM, Guicherit OR, Frölich M, Gooszen HG. Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets. Regul Pept. 1995 Dec 7;60(1):61-7. doi: 10.1016/0167-0115(95)00122-4. PMID: 8747785.

3) Metabolic control after canine islet transplantation. M.P.M. van der Burg, P.T.R. van Suylichem, O.R. Guicherit, J.H.M. van Deijnen, M. Frölich, and H.G. Gooszen (Universities of Leiden & Groningen, The Netherlands). Poster presented at the 13th Workshop of the AIDSPIT Study Group , Igls, Austria, January 23–25, 1994 •

4) Metabolic control after canine islet transplantation. Van der Burg M.P.M., Guicherit O.R., van Suylichem P.T.R., Frölich M., van Deijnen J.H.M. , Gooszen H.G. (Leiden, The Netherlands; Groningen, The Netherlands). Horm metab Res 1994; 26: 63. (Abstract). View/Download file 1MEMO_20251113_2

5) Background of this work was posted in Dutch Islets Transplant Team • @1MEMO 20250125 • URL https://michelvanderburg.com/2025/01/25/dutch-islets-transplant-team-1memo-20250125/

6) Michael P.M. van der Burg. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation. (Doctoral Thesis, Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University), Boskoop: M.P.M. van der Burg | Miracles.Media (ISBN electronic, pdf, 9789080216402 ; ISBN print 9789080216419, 9080216410), 1994: 192 p. URL Thesis Repository Leiden University https://hdl.handle.net/1887/3486604

PM – Recording of the 13th AIDSPIT seminar on lessons from clinical islet transplantation was posted yesterday (7).

7) Clinical Islet Transplantation 13th AIDSPIT • @1MEMO 20251113 • URL https://michelvanderburg.com/2025/11/13/clinical-islet-transplantation-13th-aidspit-1memo-20251113/

#GLP1 #diabetes #islets #transplant #AIDSPIT

Updates

20251127 title updated – insert : AIDSPIT 1994

Citation info : GLP-1 blood sugar regulation in islet transplants • AIDSPIT 1994 • Michel van der Burg • Miracles.Media • @1MEMO 20251114 • TakeNode 810cc881-d084-4d2e-b252-d432918b1946 • URL https://michelvanderburg.com/2025/11/14

Dutch Islets Transplant Team • @1MEMO 20250125

Islets isolated April 18, 1989 using the UW-Solution • Miracles.Media • 20250103_1 • TakeNode eeb55729-c02b-4f73-ab0e-9f71b65bf85e

Rightaway, April 1989, when we obtained these highly purified canine islets of Langerhans by introducing the UW-Solution for isolating the islets from pancreases (1,2,3), we started using these islets to study the importance of gut factors for islet transplants — the capacity of the isolated islets to secrete insulin during stimulation with glucose, other nutrients, and potentially gut hormones ( ‘incretins’).

Isolated islets in perifusion chambers

Isolated islets, not transplanted, were examined in the Leiden Islet Laboratory. The insulin secretion of these islets was measured, while the islets were housed in plastic micro-chambers , that were flushed with solutions containing various levels of glucose and gut hormones , mimicking the blood levels as found following meals in islet transplants (4).

Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911

Autotransplantation of islets

A few months later , Summer 1989, we performed a series of transplants of isolated canine islets (5) , we likewise focussed our research on the importance of gut factors in metabolic control by the islet grafts, and therefore introduced meal tests — apart from a series of intravenous tests. Both simple and convenient, such meal tests proofed to be also an excellent way to study both the capacity of the transplanted islets to secrete insulin, as well as the contribution of gut hormones – in the so-called ‘entero-insular axis’ (6).

Autotransplantation of islets in the spleen • Michel van der Burg • Miracles.Media • @1MEMO 20250125_1 • Left : Canine pancreas with two cannulas in the pancreatic ducts (for infusion of collagenase solution) , with the blood vessels clamped at the time of removal of the gland. Not shown here: After removal of the gland the collagenase solution is infused , and the pancreatic islets are isolated within a few hours. Right : Next the purified islets are returned by infusion in the spleen of the same animal (auto-transplantation). Drawings by medical artist J. Wetselaar-Whittaker — with my hand posing for the injection drawing ;)

Contribution of gut factors to canine isolated islet function ?

Spring 1990 our first results could be presented of these sophisticated islet function tests upto 3 months after islet transplantation, together with our first findings of the direct effects of the gut hormones CCK and GIP on the isolated islets in the perifusion system in the Leiden Islet Lab.

Spring meeting 1990 of the Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_2

Here the proceedings presented at the 1990 spring meeting of the Dutch Society for Gastroenterology (7).

Dutch Islets Transplant Team

October 8, 1990, Paul van Suylichem, from the Groningen islet research group, visited his alma mater again, the Leiden University on the occasion of the 3rd Symposium Experimental Surgical Research (SEOHS).
I was presenting results at the symposium on metabolic control upto 3 mo after the succesful canine islet transplants – islets isolated using the UW-Solution – known as Viaspan for the cold storage of donor organs (8,9).
Paul had started together with me in 1985 building the Leiden Islet Lab (10), that I continued from 1986 after Paul left together with project leader Reinout van Schilfgaarde starting the Groningen islet group (11).
I took the chance to invite Paul for a visit together that day in the nearby Leiden Islet Lab , for a closer look at our latest work on canine islet isolation, transplantation, and the new Percoll-UWS purification gradients (12) — and took this picture of Paul examining an islet prep at the microscope in the lab , with the Acusyst perifusion system in the background.
In late 1990, the Groningen islet team with Paul would also start this preclinical model of canine islet isolation and transplantation.

Paul van Suylichem (Groningen Islet Team) in Leiden Islet Laboratory, October 8, 1990 • Photo by Michel van der Burg • Miracles.Media • @1MEMO 20250125_3

A year later, Oct 1991, during the 5th Congress of the European Society for Organ Transplantation Congress (5th ESOT) in Maastricht (12), I learned from Paul’s co-worker Jan-Erik van Deijnen that the Groningen team, after initially several failed transplant attempts, had finally succeeded in the last 5 transplants in a row. They had mastered the technique and had started to complete this work with histology of the transplants.

We, in Leiden, had made plans earlier that summer to expand our small group of islet transplants, with a second series of transplants with a view to expanding our research on metabolic control in islet transplantation, with new sophisticated research on the effect on insulin secretion of the newly discovered gut hormone GLP-1. At the same time we would also be able to test our efficient new technique of isolation and purification of the islets in that transplantation setting.

A few days after this 5th ESOT congress it seemed better to me to refrain from new transplants in more animals, and I proposed to expand our sophisticated, functional research with research on the Groningen canine islet transplants.

Later that month, Oct 1991, islet perifusion experiments with the gut hormone GLP-1 were started (13,14,15).

And… November 1991, Paul van Suylichem’s research associate Annemiek Weemaes brought the Groningen canine transplants to Leiden, for our very successful collaborative project , with the planned additional studies in the combined Leiden and Groningen group of transplants, examining additionally insulin action (sensitivity) and the ‘incretin’ effect (stimulation of insulin secretion) of the gut hormone GLP-1. Experiments we completed in 1992 (14,16,17,18).

Notes

IMAGE 20250103_1
Islets isolated April 18, 1989 using the UW-Solution • Miracles.Media • 20250103_1 • TakeNode eeb55729-c02b-4f73-ab0e-9f71b65bf85e

1) Pancreatic Islet Isolation With UW Solution • A New Concept • Michel van der Burg • Miracles.Media • @1MEMO 20241224 • URL https://michelvanderburg.com/2024/12/24/pancreatic-islet-isolation-with-uw-solution-a-new-concept-20241224/

2) Pancreatic Islet Isolation in UW Solution & Transplantation • ESOT 1989 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20241229 • URL michelvanderburg.com/2024/12/29/

3) Pancreatic Islets UWS Series 1989 • Kodak PhotoCD • Michel van der Burg • Miracles.Media • @1MEMO 20250103 • URL michelvanderburg.com/2025/01/03/

4) Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911 • TakeNode fdf6f65c-28b7-4936-8c23-83225e6f2ff0 • URL https://michelvanderburg.com/2024/09/11/

IMAGE 20240911
Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911 • TakeNode fdf6f65c-28b7-4936-8c23-83225e6f2ff0

5) Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com • URL https://michelvanderburg.com/2024/08/30/

6) Entero Insular Axis • Michel van der Burg • Miracles.Media • @1MEMO 20250123 • URL michelvanderburg.com/2025/01/23/

IMAGE 20250125_1
Autotransplantation of islets in the spleen • Michel van der Burg • Miracles.Media • @1MEMO 20250125_1 • Left : Canine pancreas with two cannulas in the pancreatic ducts (for infusion of collagenase solution) , with the blood vessels clamped at the time of removal of the gland. Not shown here : After removal of the gland the collagenase solution is infused , and the pancreatic islets are isolated within a few hours. Right : Next the purified islets are returned by infusion in the spleen of the same animal (auto-transplantation). Drawings by medical artist J. Wetselaar-Whittaker — with my hand posing for the injection drawing ;) • TakeNode da74e6a2-e21d-4690-afe5-356949221658

IMAGE 20250125_2
Spring meeting 1990 of the Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_2 • TakeNode 65cb9de6-a111-4636-8766-d586b001d73e

7) Van der Burg MPM, Guicherit OR, Jansen JBMJ, Lamers CBHW, Scherft JP, Gooszen HG.
Contribution of gut factors to canine isolated islet function? Spring meeting of the Dutch Society for Gastroenterology (NVGE), Veldhoven (The Netherlands) March 23–24, 1990. The proceedings pdf (1MEMO_20250125_2) is available for download below.

Five years later the Dutch Society for Gastroenterology awarded the Glaxo Wellcome Gastrointestinal Research Award for this research (Ph.D. thesis “Pancreatic islet transplantation”) at the Fall meeting of the Dutch Society for Gastroenterology (NVGE), Veldhoven, The Netherlands, October 5, 1995).

Glaxo Wellcome Gastroenterology Research Award, Oct 5, 1995, Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_4 • TakeNode 3152bca6-c98e-4900-89bf-d3e241f14405

8) Van der Burg MPM, Guicherit OR, Ploeg RJ, Scherft JP, Bruijn JA, Frölich M, Prins FA, Gooszen HG. Successful canine pancreatic islet transplantation using ViaSpan. 3rd Symposium Experimental Surgical Research (SEOHS), Leiden (The Netherlands) October 8, 1990.

9) Van der Burg MPM, Gooszen HG, Ploeg RJ, Guicherit OR, Scherft JP, Terpstra JL, Frölich M. Over 90% purified canine isolated pancreatic islets using UW solution (Abstract). Neth J Surg 1990; 42: 30. Pdf abstract (1MEMO_20250125_5) is available for download below.

10) Leiden Islet Laboratory History • 20240803 | Michel van der Burg | URL michelvanderburg.com/2024/08/03/

11) Cradle of Islet Transplants • 20240829 • Michel van der Burg • URL https://michelvanderburg.com/2024/08/29/

12) Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

IMAGE 20250125_3
Paul van Suylichem (Groningen Islet Team) in Leiden Islet Laboratory, October 8, 1990 • Photo by Michel van der Burg • Miracles.Media • @1MEMO 20250125_3 • TakeNode e8ce7630-4e75-402b-a4c2-9b007a8dd61b

13) Van der Burg MPM, Guicherit OR, Scherft JP, Frölich M, Terpstra JL, Gooszen HG. Functie na intralienale transplantatie van eilandjes van Langerhans in de hond ( Function after intrasplenic transplantation of islets of Langerhans in dogs ). Surgeon days ’92 of the Dutch Surgery Society, Rotterdam (The Netherlands) May 21–22, 1992. In : Gut factors controlling pancreatic islets • 20240910 | Michel van der Burg | michelvanderburg•com

14) Michael P.M. van der Burg. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation. (Doctoral Thesis, Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University), Boskoop: M.P.M. van der Burg | Miracles.Media (ISBN electronic, pdf, 9789080216402 ; ISBN print 9789080216419, 9080216410), 1994: 192 p. URL Thesis Repository Leiden University https://hdl.handle.net/1887/3486604

15) van der Burg MPM, Guicherit OR, Frölich M, Gooszen HG. Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets. Regul Pept. 1995 Dec 7;60(1):61-7. doi: 10.1016/0167-0115(95)00122-4. PMID: 8747785.

16) Van der Burg MPM, Van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glycemic control mechanisms after canine islet autografting. 5th International Congress on Pancreas and Islet Transplantation (IPITA), Miami Beach (USA) June 18–22, 1995.

17) van der Burg MPM, van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glycemic control mechanisms after canine islet autografting. Transplant Proc. 1995 Dec;27(6):3187-8. PMID: 8539903. Download (PMID_8539903) below .

18) van der Burg MPM, van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glucoregulation after canine islet transplantation: contribution of insulin secretory capacity, insulin action, and the entero-insular axis. Cell Transplant. 1997 Sep-Oct;6(5):497-503. doi: 10.1177/096368979700600509. PMID: 9331501. Download Free PDF https://hdl.handle.net/11370/59231eab-6091-415d-8b2b-4e5e6508a978

Citation info : Dutch Islet Transplants Team • Michel van der Burg • Miracles.Media • @1MEMO 20250125 • URL michelvanderburg.com/2025/01/25/

Islet Transplants Performance 5th ESOT 1991 • @1MEMO 20250109

Islet Transplant Performance 5th ESOT 1991 • Michel van der Burg • Miracles.Media • @1MEMO 20250109_1 • TakeNode 75edbb4e-4360-43b8-8783-363ffd34c0ef

Poster (1) presented at the 5th Congress European Society for Organ Transplantation, Maastricht (The Netherlands) October 7–10, 1991. The poster was originally created on a Macintosh computer Oct 6, 1991, using the MacDraw II application, with graphs from Cricket Graph. That 1991 poster was remastered today in LibreOffice.

We presented 2 posters at the 5th ESOT, this poster (1), and another one on the effects of denervation with pancreas transplantation (2).

Two years after the 4th ESOT (in Barcelona, Nov 1989) where we introduced the UW-Solution as an islet isolation solution before density gradient purification, we now had a talk at this 5th ESOT on the use of the UW-Solution as the islet isolation solution, both before purification, and also during the purification in an innovative density gradient (3) — the foundation for current clinical purification methods. The talk was recorded on tape (except for the intro), and will be posted here soon too.

Notes

1) Van der Burg MPM, Guicherit OR, Ebert R, Jansen JBMJ, Creutzfeld W, Lamers CBHW, Frölich M, Gooszen HG. Postprandial performance after canine islet transplantation: the importance of gut factors. 5th Congress European Society for Organ Transplantation, Maastricht (The Netherlands) October 7–10, 1991.

2) Guicherit OR, Van der Burg MPM, Lemkes HHPJ, Frölich M, Gooszen HG. Pancreatic
denervation causes reduced insulin sensitivity. 5 th Congress European Society for Organ Transplantation, Maastricht (The Netherlands) Oct 7–10 1991.

3) Van der Burg MPM, Guicherit OR, Prins FA, Scherft JP, Frölich M, Gooszen HG. Percoll in UW: efficient iso-osmotic canine and human islet purification. 5th Congress European Society for Organ Transplantation, Maastricht (The Netherlands) October 7–10, 1991.

Citation info : Islet Transplant Performance 5th ESOT 1991 • Michel van der Burg • Miracles.Media • @1MEMO 20250109 • URL michelvanderburg.com/2025/01/09/