Tagged: Dpp-4

Diabetes and Parkinson’s

A reader recently asked for an explanation of some recent research regarding diabetes and Parkinson’s.

You see, a significant proportion of the Parkinson’s community have glucose intolerance issues and some live with the added burden of diabetes. That said, the vast majority of diabetics do not develop PD. Likewise, the vast majority of people with Parkinson’s do not have a diagnosis of diabetes.

There does appear to be a curious relationship between Parkinson’s and diabetes, with some recent research suggests that this association can be detrimental to the course of the condition. 

In today’s post we will look at what what diabetes is, consider the associations with Parkinson’s, and we will discuss the new research findings.


Foreman and Ali. Source: Voanews

1974 was an amazing year.

On October 30th, the much-hyped heavyweight title match – the ‘Rumble in the Jungle’ – between George Foreman and Muhammad Ali took place in Kinshasa, Zaire (Democratic Republic of the Congo).

Stephen King. Source: VanityFair

A 26-year-old author named Stephen King published his debut novel, “Carrie” (April 5, with a first print-run of just 30,000 copies).

Lucy. Source: Youtube

The fossil remains of a 3.2 million years old hominid skeleton was discovered in Ethiopia (November 24th). It was named ‘Lucy’ – after the song “Lucy in the Sky with Diamonds” by The Beatles which was played repeatedly in the expedition camp the evening after the team’s first day of work on the site (Source).

And Richard Nixon becomes the first US president to resign from office (August 9th).

President Richard Nixon. Source: Fee

In addition to all of this, in December of 1974, a small study was published in the Journal of Chronic Diseases.

It dealt with Parkinson’s and it presented a rather startling set of findings:

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PACAP and a snail model of Parkinson’s

We are going to talk about a snail model of Parkinson’s disease. I kid you not.

Love them or hate them, recent research on snails is helping us to better understand a potential therapeutic target for Parkinson’s disease, called Pituitary adenylate cyclase-activating polypeptide (or PACAP).

In today’s post we will look at what PACAP is, outline the new snail research, and discuss what they mean for people living with Parkinson’s disease.


Snail2

The humble snail. Source: Warrenphotographic

In a recent post, I talked about a class of drugs called Dipeptidyl peptidase-4 (or DPP-4) inhibitors (Click here to read that post). DPP-4 is a ubiquitous enzyme (it is present on most cells in your body) that breaks down certain proteins.

In that post, I listed some of the proteins that DPP-4 targets – they include:

  • Gastrin-releasing peptide (GRP)
  • Glucagon
  • Glucagon-like peptide-1 (GLP-1)
  • Glucagon-like peptide-2 (GLP-2)
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF)
  • GHRH and IGF-1
  • High-mobility group box 1 (HMGB1)
  • Macrophage-derived chemokine (MDC)
  • Macrophage inflammatory protein-1 α (MIP-1 α), chemokine (C-C motif) ligand 3-like 1 (CCL3L1), or LD78β
  • Pituitary adenylate cyclase-activating polypeptide (PACAP)
  • Neuropeptide Y (NPY)
  • Regulated on activation, normal T cell expressed and secreted (Rantes)
  • Stromal cell-derived factor-1 (SDF-1)
  • Substance P (SP)

Lots of interesting proteins with regards to Parkinson’s disease on this list, including GLP-1 which has been turned in the drug Exenatide (which has demonstrated positive effects in recent clinical trials for Parkinson’s disease – click here and here to read more about this). Another interesting protein on the list is ‘Granulocyte-macrophage colony-stimulating factor‘ (GM-CSF) which we have also discussed in a previous post (Click here to read that post). A synthetic version of GM-CSF (called Sargramostim) has recently been tested in a clinical trial of Parkinson’s disease in Nebraska, and the results of that Phase I trial have been very encouraging.

By treating people with DPP-4 inhibitors (also known as ‘gliptins’), one would be blocking the breaking down of these potentially beneficial proteins – increasing the general amount of GLP-1 and GMCSF that is floating around in the body.


EDITOR’S NOTE: DPP-4 inhibitors have not yet been clinically tested in Parkinson’s disease, and thus we have no idea if they are safe in people with this condition. They are being mentioned here purely as part of an academic discussion.


One protein on the list of DPP-4 targets above that we have not yet discussed is Pituitary adenylate cyclase-activating polypeptide (or PACAP).

And today we are going to have a look at it.

Why?

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DPP-4: Not a Star Wars character

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Dipeptidyl peptidase-4 (or DPP-4) is an enzyme that breaks down the protein (GLP-1) that stimulates insulin release in your body. 

Inhibitors of DPP-4 are used in the treatment of Type 2 diabetes, because they help increase insulin levels in the body.

Recently some Swedish researchers noticed something curious about DPP-4 inhibitors: They appear to reduce the risk of developing Parkinson’s disease.

In today’s post, we will review what DPP-4 inhibitors do and look at how this could be reducing the risk of Parkinson’s disease.


januvia

Sitagliptin. Source: Diabetesmedicine

Last year an interesting research report about a class of medications that could possibly reduce the risk of developing Parkinson’s disease was published in the journal Movement disorders:

SWeds

Title: Reduced incidence of Parkinson’s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study.
Authors: Svenningsson P, Wirdefeldt K, Yin L, Fang F, Markaki I, Efendic S, Ludvigsson JF.
Journal: Movement Disorders 2016 Jul 19.
PMID: 27431803

In this study, the investigators used the Swedish Patient Register, to find the medical records of 980 people who were diagnosed with Parkinson’s disease but also had type 2 diabetes. Importantly, all of the subjects had been treated with Type 2 diabetes medication for at least 6 months prior to the date of Parkinson’s being diagnosed.

For comparative sake, they selected 5 controls (non-Parkinsonian) with Type 2 diabetes (n = 4,900) for each of their Parkinsonian+diabetes subjects. They next looked at whether GLP-1R agonists (such as Exenatide), Dipeptidyl peptidase-4 (or DPP-4) inhibitors, or any other oral Type 2 diabetic medication can influence the incidence of Parkinson’s disease.

Now, if all things are considered equal, then when looking at each diabetes medication there should be 1 person in the Parkinson’s disease + Type 2 diabetes for every 5 people in the Type 2 diabetes control group taking each medication right? That is because there are almost 1000 people in the first group and 5000 in the second group.

But this is not what the researchers found.

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