Comments on: The Discovery of Insulin http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/ A site dedicated to solving diabetes. Sat, 14 Aug 2010 23:12:33 +0000 http://wordpress.org/?v=2.9.2 hourly 1 By: Scott S http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/comment-page-1/#comment-2345 Scott S Wed, 23 Jun 2010 21:19:17 +0000 http://www.solvingdiabetes.org/?p=230#comment-2345 You might consider adding "Invisible Frontiers: The Race to Synthesize a Human Gene" by Stephen S. Hall to your list of classics regarding type 1 diabetes. Its a story of how biosynthetic "human" insulin (its not really human, no more than artificial vanilla is the same as real vanilla to a chef) was created and the various challenges and lengths that were gone through to create it, and the story of big egos and whatnot that were involved in doing this. A classic that should be added to the list; now out-of-print, but should be available via your local library without too much trouble. You might consider adding “Invisible Frontiers: The Race to Synthesize a Human Gene” by Stephen S. Hall to your list of classics regarding type 1 diabetes. Its a story of how biosynthetic “human” insulin (its not really human, no more than artificial vanilla is the same as real vanilla to a chef) was created and the various challenges and lengths that were gone through to create it, and the story of big egos and whatnot that were involved in doing this. A classic that should be added to the list; now out-of-print, but should be available via your local library without too much trouble.

]]> By: JPMarat http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/comment-page-1/#comment-32 JPMarat Tue, 14 Jul 2009 17:13:50 +0000 http://www.solvingdiabetes.org/?p=230#comment-32 C-Peptide supplementation seems to harm type 2 diabetics by promoting atherosclerosis, since they already have too much insulin and too much c-peptide in the circulation. (D. Walcher and N. Marx, "Advanced Glycation End Products and C-Peptide Modulators," Seminars in Immunopathology, 31(1) 103 (2009); L. Nordquist and M. Johansson,"Proinsulin C-Peptide: Friend or Foe in the Development of Diabetic Complications?" Vascular Health Risk Management, 4(6) 1288 (2008)) But in type 1 diabetics, c-peptide supplementation seems to improve nerve function, limit the progression of incipient nephropathy, and promote microcirculation. (B. Johansson, et al, "Beneficial Effects of C-Peptide in Incipient Nephropathy in Patients with Type 1 Diabetes Mellitus," Diabetes Medicine, 17(3) 181 (2001); J. Wahren, et al, "Role of C-Peptide in Human Physiology," American Journal of Physiology, Endocrinology, and Metabolism, 278(5) E759-68 (2008); J. Wahren, "C-Peptide: New Findings and Therapeutic Implications in Diabetes," Clincial Physiology and Functional Imaging, 24(4) 180 (2004); K. Ekberg, et al, "C-Peptide Replacement Therapy and Sensory Nerve Function in TYpe 1 Diabetic Neuropathy," Diabetes Care, 30(1) 71 (2007); T. Forst, et al, "Role of C-Peptide in the Regulation of Microvascular Blood Flow," Experimental Diabetes Research, 176245 (2008) Article ID 384219) One company has been working for years to commercialize an injectable c-peptide product for diabetics, but progress has been unaccountably slow. Human c-peptide of injectable quality can already be obtained from chemical supply companies, and the appropriate replacement dose for type 1 diabetics has already been narrowed down to 1.5 mg to 4.5 mg/day in four divided doses. However, since the latest prices I have seen for it amount to about $200 per mg, and I don't happen to have a spare $320,000 a year to spend on it at the moment, it will be some time before I can report the results of any experimental trial on myself. It speaks volumes about the negative effects of the tunnel vision of most researchers, who have been obsessed with blood glucose control to the exclusion of all other possible methods to interrupt the long chain of events causing diabetic complications, that early studies of c-peptide in the 1980s dismissed it as useless because it did not improve blood sugar control! Preventing complications by lowering blood sugar levels is difficult to achieve, costs a huge amount of time and energy, and can cause lethal or permanently damaging episodes of severe hypoglycemia, but few seem prepared to address these problems by finding ways other than blood sugar control to reduce diabetic complications. C-Peptide supplementation seems to harm type 2 diabetics by promoting atherosclerosis, since they already have too much insulin and too much c-peptide in the circulation. (D. Walcher and N. Marx, “Advanced Glycation End Products and C-Peptide Modulators,” Seminars in Immunopathology, 31(1) 103 (2009); L. Nordquist and M. Johansson,”Proinsulin C-Peptide: Friend or Foe in the Development of Diabetic Complications?” Vascular Health Risk Management, 4(6) 1288 (2008))

But in type 1 diabetics, c-peptide supplementation seems to improve nerve function, limit the progression of incipient nephropathy, and promote microcirculation. (B. Johansson, et al, “Beneficial Effects of C-Peptide in Incipient Nephropathy in Patients with Type 1 Diabetes Mellitus,” Diabetes Medicine, 17(3) 181 (2001); J. Wahren, et al, “Role of C-Peptide in Human Physiology,” American Journal of Physiology, Endocrinology, and Metabolism, 278(5) E759-68 (2008); J. Wahren, “C-Peptide: New Findings and Therapeutic Implications in Diabetes,” Clincial Physiology and Functional Imaging, 24(4) 180 (2004); K. Ekberg, et al, “C-Peptide Replacement Therapy and Sensory Nerve Function in TYpe 1 Diabetic Neuropathy,” Diabetes Care, 30(1) 71 (2007); T. Forst, et al, “Role of C-Peptide in the Regulation of Microvascular Blood Flow,” Experimental Diabetes Research, 176245 (2008) Article ID 384219)

One company has been working for years to commercialize an injectable c-peptide product for diabetics, but progress has been unaccountably slow. Human c-peptide of injectable quality can already be obtained from chemical supply companies, and the appropriate replacement dose for type 1 diabetics has already been narrowed down to 1.5 mg to 4.5 mg/day in four divided doses. However, since the latest prices I have seen for it amount to about $200 per mg, and I don’t happen to have a spare $320,000 a year to spend on it at the moment, it will be some time before I can report the results of any experimental trial on myself.

It speaks volumes about the negative effects of the tunnel vision of most researchers, who have been obsessed with blood glucose control to the exclusion of all other possible methods to interrupt the long chain of events causing diabetic complications, that early studies of c-peptide in the 1980s dismissed it as useless because it did not improve blood sugar control! Preventing complications by lowering blood sugar levels is difficult to achieve, costs a huge amount of time and energy, and can cause lethal or permanently damaging episodes of severe hypoglycemia, but few seem prepared to address these problems by finding ways other than blood sugar control to reduce diabetic complications.

]]> By: Scott King http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/comment-page-1/#comment-31 Scott King Mon, 13 Jul 2009 19:07:36 +0000 http://www.solvingdiabetes.org/?p=230#comment-31 I must politely disagree on the purity of insulin. When I was first diagnosed I started on then-standard Lilly pig insulin. Highly purified insulin's did not become standard until the 1980's. My first insulin had enough lipase to damage the fat cells at the injection site, so so I still have divots in my skin. But if there were zero lipase and equimolar c-peptide that would be OK. I am of two minds about the c-peptide claims. On the one hand it is naturally secreted with insulin in equimolar amounts, suggesting it has some function. On the other hand c-peptides between species rapidly diverge, whereas insulin is highly conserved, suggesting that the c-peptide function is not specific or maybe non-existent. The Ido paper is intriguing, but it was twelve years ago, in rats. Can you cite a c-peptide clinical study you find persuasive? I have not seen one. Lots of people were looking for the anti-diabetes factor in the pancreas in the early 20th century. It think it shows how primitive protein chemistry was. Nowadays it would be solved in months, if not a week. I must politely disagree on the purity of insulin. When I was first diagnosed I started on then-standard Lilly pig insulin. Highly purified insulin’s did not become standard until the 1980’s. My first insulin had enough lipase to damage the fat cells at the injection site, so so I still have divots in my skin. But if there were zero lipase and equimolar c-peptide that would be OK.

I am of two minds about the c-peptide claims. On the one hand it is naturally secreted with insulin in equimolar amounts, suggesting it has some function. On the other hand c-peptides between species rapidly diverge, whereas insulin is highly conserved, suggesting that the c-peptide function is not specific or maybe non-existent. The Ido paper is intriguing, but it was twelve years ago, in rats. Can you cite a c-peptide clinical study you find persuasive? I have not seen one.

Lots of people were looking for the anti-diabetes factor in the pancreas in the early 20th century. It think it shows how primitive protein chemistry was. Nowadays it would be solved in months, if not a week.

]]> By: JPMarat http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/comment-page-1/#comment-30 JPMarat Sun, 12 Jul 2009 19:18:16 +0000 http://www.solvingdiabetes.org/?p=230#comment-30 It is interesting that after von Mehring and Minkowski conclusively demonstrated in Berlin in 1889 that diabetes was caused by a lack of something that the pancreas was producing, it took another 32 years to isolate a clinically effective sample of what this was. Zuelzer and Paulescu probably isolated insulin before Banting and Best did, but Zuelzer stopped using it on patients after he found it caused what he thought was a massive anaphylactic shock, which was in fact probably severe hypoglycemia, and Paulescu later claimed he forgot about developing his discovery because "he was distracted by World War I." Admittedly, World War I was interesting, but one could have hoped that that a scientist would have found improving the lot of diabetics equally interesting. I am not sure that the ultimate purification of insulin was entirely a good thing, however. The early, impure samples of insulin used contained about 10% c-peptide, which came to be regarded as a useless metabolic by-product of insulin production. Recently, however, researchers have found that it may well hold the key to preventing diabetic complications, independently of the blood sugar control achieved by insulin treatment. See: Y. Ide, et al, "Prevention of Vascular and Neuronal Destruction in Diabetic Rats by C-Peptide," Science, 277(5325) 563 (1997). It is interesting that after von Mehring and Minkowski conclusively demonstrated in Berlin in 1889 that diabetes was caused by a lack of something that the pancreas was producing, it took another 32 years to isolate a clinically effective sample of what this was. Zuelzer and Paulescu probably isolated insulin before Banting and Best did, but Zuelzer stopped using it on patients after he found it caused what he thought was a massive anaphylactic shock, which was in fact probably severe hypoglycemia, and Paulescu later claimed he forgot about developing his discovery because “he was distracted by World War I.” Admittedly, World War I was interesting, but one could have hoped that that a scientist would have found improving the lot of diabetics equally interesting.

I am not sure that the ultimate purification of insulin was entirely a good thing, however. The early, impure samples of insulin used contained about 10% c-peptide, which came to be regarded as a useless metabolic by-product of insulin production. Recently, however, researchers have found that it may well hold the key to preventing diabetic complications, independently of the blood sugar control achieved by insulin treatment. See: Y. Ide, et al, “Prevention of Vascular and Neuronal Destruction in Diabetic Rats by C-Peptide,” Science, 277(5325) 563 (1997).

]]> By: Olivia Kuser http://www.solvingdiabetes.org/2009/06/25/the-discovery-of-insulin/comment-page-1/#comment-15 Olivia Kuser Mon, 06 Jul 2009 02:26:55 +0000 http://www.solvingdiabetes.org/?p=230#comment-15 Dear Scott- Thank you for continuing this important work. My mother, grandmother and aunt all had Type II diabetes and i have just been diagnosed with pre-diabetes. I realize this is a seriously different animal than Type I diabetes- still, I am now personally interested in all diabetes research. Olivia Dear Scott-
Thank you for continuing this important work. My mother, grandmother and aunt all had Type II diabetes and i have just been diagnosed with pre-diabetes. I realize this is a seriously different animal than Type I diabetes- still, I am now personally interested in all diabetes research.
Olivia

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