unOC linked to Diabetes relief

GLP-1 effects on different human organs.
Photo credits: Daniel J. Drucker (author of the paper of
DOI: 10.1016/j.cmet.2006.01.004)

Researchers have perhaps found another means by which to manage type 2 diabetes. A group from 九州大学 (Kyushu  University) has shown that addition of uncarboxylated osteocalcin (unOC) stimulates glucagon-like peptide-1 (GLP-1) release and insulin secretion in mice.

GLP-1 is normally released in released into the blood in response to eating, so that insulin can be released and digested glucose can be taken into cells. In those with type-II diabetes, the insulin release pathway is impaired in some way, so insufficient insulin (or no insulin) is produced to promote glucose uptake.

UnOC has shown in previous studies to have an effect on the pancreas directly to stimulate insulin release; therefore, this study wanted to test the indirect effect of unOC on insulin secretion via the GLP-1 pathway.

Using mice, unOC’s effect on GLP-1 secretion was tested. 20 minutes after giving mice unOC orally or intraperitoneally, a maximal rise of 50 pg/mL of serum GLP-1 was seen. However, this significant rise was only seen in mice also given the DPP-IV inhibitor sitgaliptin. This needed to be co-administered because GLP-1 has a very short half life and would breakdown before the effects could be seen.

Extending from this, the insulin levels in mice given unOC were seen as raised as well. With the combination of unOC and sitagliptin, insulin rose (maximally) 0.4 ng/mL. These results were seen administering therapies orally or via intrapineal injection. Administering intravenously gave similar results with significant rises in GLP-1 and insulin sooner (as expected).

This study shows unOC may be a strong therapy for type II diabetes management if given to patients in the pure chemical form, as an additive to food, or the like.

Akiko Mizokami, Yu Yasutake, Jing Gao, Miho Matsuda, Ichiro Takahashi, Hiroshi Takeuchi, Masato Hirata. Osteocalcin Induces Release of Glucagon-Like Peptide-1 and Thereby Stimulates Insulin Secretion in Mice. PLoS ONE, 2013.


A note from me:

Lately my writings have been sluggishly drawn out and without the wherewithal to inspire (not to mention I’ve been posting suuuuuper late). Because of this, I’m taking a week break from blogging. For those that follow: I’ll see you on March 1st. For those that stumbled upon this today: Hopefully you’ll muse my articles, learn some cool stuff, and come back in a week when I pick up again.

See you all seven mornings from now 🙂


Restoring insulin creation in diabetes type I sufferers

Type I diabetes is very manageable by taking daily doses of exogenous insulin. However, researchers of the University of South Dakota pulled together a method utilizing G-protein coupled receptor 119 (GPR119) and dipeptidylpeptidase-IV (DPP-IV) to regenerate lost ß-islet cells of diabetics and restore insulin production in the body.

ß-cells are the insulin generators of the body, but in type I diabetes patients, they don’t exist or don’t work. GPR119, when activated by an agonist such as PSN632408, stimulates ß-cell replication, increases GLP-1 secretion, reduces food intake, and decreases body weight gain. If hyperstimulated in type I diabetes sufferers the level of insulin reached would be closer to that of normal body levels, which is why this was a target of this study. Contrarily, DPP-IV works to degrade or breakdown GLP-1, which is a protein that stimulates insulin release from ß-cells, enhances ß-cell proliferation, and prevents ß-cell programmed cell death.

In the study, diabetic mice with blood glucose levels of 400 to 500 mg/dL were treated with PSN632408 and/or sitagliptin for 7 weeks. The former acted as a GPR119 agonist and the latter as a DPP-IV inhibitor. After treatment ended, the three different treatment groups obtained the following percentages of normoglycemia (blood glucose < 200 mg/dL) mice:

– PSN632408, 32% mice with normoglycemia
– Sitagliptin, 36% mice with normoglycemia
– PSN632408 & sitagliptin, 59% mice with normoglycemia

The average drop in blood glucose was 257 mg/dL after seven weeks. The treatment actively reversed type I diabetes in these mice.

Further tests showed increased levels of GLP-1 (7.6±0.4 pmol/L in control mice, 14.8±1.0, 35.9±8.6, 44.2±10.5 pmol/L in mice treated with PSN632408, Sitagliptin, or both respectively), ß-cell replication, and ß-cell regeneration.

Mice treated with a GRP119 agonist and DPP-IV inhibitor showed increased ß-cell regeneration and overall insulin production. As mice have similar GRP119/DPP-IV pathways to humans, these results are very exciting for the diabetes scene.

Drinking (or painfully auto-injecting) daily insulin may no longer be necessary for diabetics if the GRP119 agonist/DPP-IV inhibitor treatment is approved for clinical use.

Ansarullah, Yan Lu, Martha Holstein, Brittany DeRuyter, Alex Rabinovitch, Zhiguang Guo. Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor. PLoS ONE, 2013.

Obesity regulator associated with pancreatic cancer risk

Human Pancreas Photo courtesy of  the Society for Endocrinology

Human Pancreas
Photo courtesy of the Society for Endocrinology

A recent study was done to find the link between circulating levels adiponectin and risk of developing pancreatic cancer. Adiponectin is a hormone associated with destroying fat derivatives, blocking endogenous glucose creation, and weight loss. A Boston based case-control study found varying levels of this hormone associated with pancreatic cancer incidence in cohorts.

Health Professionals Follow-up Study, Nurses’ Health Study, Physicians’ Health Study, Women’s Health Initiative, and Women’s Health Study were the five cohorts, resulting in 1080 subjects matched as the control against 468 pancreatic cancer case subjects. The subjects were matched by cohort, year of birth, smoking status, fasting status, and month of blood draw.

Analysis of the study revealed lower median levels of adiponectin in patients’ blood, 6.2 µg/mL, as opposed to control subjects, 6.8 µg/mL. These results were very significant with a statistical P-value of 0.009. This depicts lower levels of adiponectin as linked to higher risk of pancreatic cancer consistently across all studied cohorts and independent of other insulin resistance markers (type II diabetes, higher BMI, and normal to increased plasma C-peptide levels).

Compared with the bottom quintile (Q1) participants who had the lowest adiponectin, higher levels of adiponectin were associated with lower risk of cancer. Specifically, participants’ likelyhood of developing cancer vs. not (Odds Ratio) were:

Q2: Odds ratio of 0.61 for cancer, 95% confidence interval from 0.43 to 0.86.
Q3: Odds ratio of 0.58 for cancer, 95% confidence interval from 0.41 to 0.84.
Q4: Odds ratio of 0.59 for cancer, 95% confidence interval from 0.40 to 0.87.
Q5: Odds ratio of 0.66 for cancer, 95% confidence interval from 0.44 to 0.97.

Quintile analysis had a trend P-value of 0.04 indicating significance.

This shows that low prediagnostic levels of plasma adiponectin are indeed associated with higher risk of developing pancreatic cancer.

Although this is not the end all diagnostic result for early pancreatic cancer detection and treatment, it proves useful to have another marker to help in the fight.

Ying Bao, Edward L. Giovannucci, Peter Kraft, Meir J. Stampfer, Shuji Ogino, Jing Ma, Julie E. Buring, Howard D. Sesso, I-Min Lee, John Michael Gaziano, Nader Rifai, Michael N. Pollak, Barbara B. Cochrane, Virginia Kaklamani, Jennifer H. Lin, JoAnn E. Manson, Charles S. Fuchs and Brian M. Wolpin. 2012. A Prospective Study of Plasma Adiponectin and Pancreatic Cancer Risk in Five US Cohorts. Journal of the National Cancer Institute.