CANNABIS AND Diabetes

 

Excerpt from www.diabetes.ca:

 

Diabetes Facts

More than 9 million Canadians are living with diabetes or prediabetes

There are three main types of diabetes. Type 1 diabetes, usually diagnosed in children and adolescents, occurs when the pancreas is unable to produce insulin. Insulin is a hormone that controls the amount of glucose in the blood. Approximately 10 per cent of people with diabetes have type 1 diabetes.

The remaining 90 per cent have type 2 diabetes, which occurs when the pancreas does not produce enough insulin or when the body does not effectively use the insulin that is produced. Type 2 diabetes usually develops in adulthood, although increasing numbers of children in high-risk populations are being diagnosed.

A third type of diabetes, gestational diabetes, is a temporary condition that occurs during pregnancy. It affects approximately 2 to 4 per cent of all pregnancies (in the non-Aboriginal population) and involves an increased risk of developing diabetes for both mother and child.

Prediabetes refers to a condition where a person’s blood glucose levels are higher than normal, but not yet high enough to be diagnosed as type 2 diabetes. 


Is diabetes serious?

If left untreated or improperly managed, diabetes can result in a variety of complications, including:

  • Heart disease
  • Kidney disease
  • Eye disease
  • Problems with erection (impotence)
  • Nerve damage

The first step in preventing or delaying the onset of these complications is recognizing the risk factors, as well as signs and symptoms of diabetes.

What are the risk factors for diabetes?

If you are aged 40 or older, you are at risk for type 2 diabetes and should be tested at least every three years. If any of the following risks factors apply, you should be tested earlier and/or more often.

Being:

  • A member of a high-risk group (Aboriginal, Hispanic, Asian, South Asian or African descent)
  • Overweight (especially if you carry most of your weight around your middle)

Having:

  • A parent, brother or sister with diabetes
  • Health complications that are associated with diabetes
  • Given birth to a baby that weighed more than 4 kg (9 lb)
  • Had gestational diabetes (diabetes during pregnancy)
  • Impaired glucose tolerance or impaired fasting glucose
  • High blood pressure
  • High cholesterol or other fats in the blood
  • Been diagnosed with polycystic ovary syndrome, acanthosis nigricans (darkened patches of skin), or schizophrenia

What are the symptoms?

Signs and symptoms of diabetes include the following:

  • Unusual thirst
  • Frequent urination
  • Weight change (gain or loss)
  • Extreme fatigue or lack of energy
  • Blurred vision
  • Frequent or recurring infections
  • Cuts and bruises that are slow to heal
  • Tingling or numbness in the hands or feet
  • Trouble getting or maintaining an erection

It is important to recognize, however, that many people who have type 2 diabetes may display no symptoms.

Can you prevent diabetes?

Scientists believe that lifestyle changes can help prevent or delay the onset of type 2 diabetes. A healthy meal plan, weight control and physical activity are important prevention steps.

How is diabetes treated?

People with diabetes can expect to live active, independent and vital lives if they make a lifelong commitment to careful diabetes management, which includes the following:

  • Education: Diabetes education is an important first step. All people with diabetes need to be informed about their condition.
  • Physical Activity: Regular physical activity helps your body lower blood glucose levels, promotes weight loss, reduces stress and enhances overall fitness.
  • Nutrition: What, when and how much you eat all play an important role in regulating blood glucose levels.
  • Weight Management: Maintaining a healthy weight is especially important in the management of type 2 diabetes.
  • Medication: Type 1 diabetes is always treated with insulin. Type 2 diabetes is managed through physical activity and meal planning and may require medications and/or insulin to assist your body in controlling blood glucose more effectively.
  • Lifestyle Management: Learning to reduce stress levels in day-to-day life can help people with diabetes better manage their disease.

Blood Pressure: High blood pressure can lead to eye disease, heart disease, stroke and kidney disease, so people with diabetes should try to maintain a blood pressure level at or below 130/80. To do this, you may need to change your eating and physical activity habits and/or take medication.

Expression of Cannabinoid CB1 Receptors in Models of Diabetic Neuropathy

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Author Affiliations

  • School of Life Sciences, Napier University, Edinburgh, Scotland (F.Z., V.S., P.J.W.S.); and Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (S.H.)
  • Address correspondence to:
Dr. Paula J. W. Smith, School of Life Sciences, Napier University, 10 Colinton Rd., Edinburgh, Scotland, UK EH10 5DT. E-mail: [email protected]

Abstract

A clearer understanding of the mechanisms underlying the development and progression of diabetic neuropathy is likely to indicate new directions for the treatment of this complication of diabetes. In the present study we investigated the expression of cannabinoid CB1 receptors in models of diabetic neuropathy. PC12 cells were differentiated into a neuronal phenotype with nerve growth factor (NGF) (50 ng/ml) in varying concentrations of glucose (5.5–50 mM). CB1 receptor expression was studied at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level via immunohistochemical and Western blot analysis. CB1 expression was also compared in dorsal root ganglia (DRG) removed from streptozotocin-induced diabetic rats versus control animals. Total neurite length induced by NGF was reduced in cells cultured in 20 to 50 mM glucose at day 6 (P < 0.01 versus 5.5 mM; n = 6). Cell viability assays conducted in parallel on day 6 confirmed that the total cell numbers were not significantly different among the various glucose concentrations (P = 0.86; n = 12). RT-PCR, immunohistochemical, and Western blot analysis all revealed down-regulation of the CB1 receptor in cells treated with high glucose (P < 0.05; n = 4–5 for each), and in DRG removed from diabetic rats compared with controls (P < 0.01; n = 5 for immunohistochemistry, and n = 3 for Western blot). These results suggest that high glucose concentrations are associated with decreased expression of CB1 receptors in nerve cells. Given the neuroprotective effect of cannabinoids, a decline in CB1 receptor expression may contribute to the neurodegenerative process observed in diabetes.

 

https://jpet.aspetjournals.org/content/323/2/508.short

Am J Pathol. 2012 Feb;180(2):432-42. doi: 10.1016/j.ajpath.2011.11.003. Epub 2011 Dec 5.

 

The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications.

Horváth B, Mukhopadhyay P, Haskó G, Pacher P.

Source

Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, MSC-9413, Bethesda, MD 20892-9413, USA. [email protected]

 

Abstract

Oxidative stress and inflammation play critical roles in the development of diabetes and its complications. Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions. The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications. This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system. The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.

Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID: 22155112 [PubMed – indexed for MEDLINE] PMCID: PMC3349875

 

https://www.ncbi.nlm.nih.gov/pubmed/22155112

Cannabinoids Inhibit Insulin Receptor Signaling in Pancreatic β-Cells

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Author Affiliations

  • 1National Institute on Aging/NIH, Baltimore, Maryland
  • 2Division of Endocrinology, Johns Hopkins Medical Institutes, Baltimore, Maryland
  • 3Department of Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts

 

Abstract

OBJECTIVE Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting β-cells in the islets of Langerhans. Insulin itself positively regulates β-cell proliferation in an autocrine manner through the insulin-receptor (IR) signaling pathway. It is now coming to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate β-cell proliferation and if they influence insulin action.

RESEARCH DESIGN AND METHODS We measured EC production in isolated human and mouse islets and β-cell line in response to glucose and KCl. We evaluated human and mouse islets, several β-cell lines, and CB1R-null (CB1R−/−) mice for the presence of a fully functioning EC system. We investigated if ECs influence β-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice.

RESULTS ECs are generated within β-cells, which also express CB1Rs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CB1R results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in β-cells and leads to increased β-cell proliferation and mass. CB1R antagonism in db/db mice results in reduced blood glucose and increased β-cell proliferation and mass, coupled with enhanced IR signaling in β-cells. Furthermore, CB1R activation impedes insulin-stimulated IR autophosphorylation on β-cells in a Gαi-dependent manner.

CONCLUSIONS These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of β-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and proliferation in diabetes.

 

https://diabetes.diabetesjournals.org/content/early/2011/02/20/db10-1550

The role of cannabis and cannabinoids in diabetes

  • Simon White
    1. School of Pharmacy, Keele University, Keele, Staffordshire, UK
  • Gabor Varbiro
    1. School of Pharmacy, Keele University, Keele, Staffordshire, UK
  • Carolyn Voisey
    1. School of Pharmacy, Keele University, Keele, Staffordshire, UK
  • Dhaya Perumal
    1. School of Pharmacy, Keele University, Keele, Staffordshire, UK
  • Ilana Crome
    • Academic Psychiatry, Keele University, Keele, Staffordshire, UK
  • Nazmeen Khideja
    • School of Pharmacy, Keele University, Keele, Staffordshire, UK
  • James Bashford
    • School of Pharmacy, Keele University, Keele, Staffordshire, UK

 

Abstract

This paper reviews the role of cannabis in diabetes. Cannabis is by far the most commonly used illicit drug in Britain, though its use may be declining. There are an estimated 50,000—100,000 people with diabetes using cannabis, with an unknown number using the drug for self-medication. The evidence of the effects of cannabis on diabetes is complex, ranging from anecdotal reports of benefits and harms to experimental research on cannabinoids. The endocannabinoid system appears to have a role in the regulation of body weight and food intake, and the development of hyperglycaemia, insulin resistance and dyslipidaemia. In experimental models, the main psychoactive constituent of herbal cannabis, Δ9-tetrahydrocannabinol, has been shown to interfere with both the action of insulin and its release. The paper also considers the effects of cannabis on complications of diabetes. Experimental work has suggested a mechanism to reduce neuropathy but the only double-blind clinical trial to date of a cannabis-based drug found no difference in the ability of the cannabis-based product to relieve neuropathic pain when compared with placebo. In conclusion, new insights into the role of cannabis and cannabinoids in diabetes are emerging from this developing field of research.

 

https://dvd.sagepub.com/content/10/6/267.abstract

Handb Exp Pharmacol. 2011;(203):75-104. doi: 10.1007/978-3-642-17214-4_4.

 

Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes.

Di Marzo V, Piscitelli F, Mechoulam R.

Source

Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34 Comprensorio Olivetti, 80078, Pozzuoli, NA, Italy.

 

Abstract

The cannabinoid receptors for Δ(9)-THC, and particularly, the CB(1) receptor, as well as its endogenous ligands, the endocannabinoids anandamide and 2-arachidonoylglycerol, are deeply involved in all aspects of the control of energy balance in mammals. While initially it was believed that this endocannabinoid signaling system would only facilitate energy intake, we now know that perhaps even more important functions of endocannabinoids and CB(1) receptors in this context are to enhance energy storage into the adipose tissue and reduce energy expenditure by influencing both lipid and glucose metabolism. Although normally well controlled by hormones and neuropeptides, both central and peripheral aspects of endocannabinoid regulation of energy balance can become dysregulated and contribute to obesity, dyslipidemia, and type 2 diabetes, thus raising the possibility that CB(1) antagonists might be used for the treatment of these metabolic disorders. On the other hand, evidence is emerging that some nonpsychotropic plant cannabinoids, such as cannabidiol, can be employed to retard β-cell damage in type 1 diabetes. These novel aspects of endocannabinoid research are reviewed in this chapter, with emphasis on the biological effects of plant cannabinoids and endocannabinoid receptor antagonists in diabetes.

PMID: 21484568 [PubMed – indexed for MEDLINE]

 

https://www.ncbi.nlm.nih.gov/pubmed/21484568

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