Pathophysiology and Management of Diabetes: A Review

 

Vandna Dewangan*, Himanshu Pandey

Department of  Pharmacology, Columbia Institute of Pharmacy, Tekari, Near Vidhansabha, Raipur-493111(C.G.) India.

 

ABSTRACT:

Diabetes mellitus is a very common metabolic disorder of endocrine system, every year large Number of people suffered from diabetes. According to recent survey in India about 50.8 million people are suffered from diabetes in 2010, and it will rise to 87.0 million till 2030. For the management and prevention of type 1 and type 2 diabetes different approaches have been done throughout the time In this article we have briefly discuss about evaluation of anti-diabetic activity by the use of different in vivo methods including animal model and in vitro method with special reference to cell line techniques. Article also reflect the evaluation of various anti diabetics phytoconstituents which is obtain from different plant source their activity, mechanism of action and it also highlight the advancement that has been done in past few year by different scientist their work title in different beta cell line technique and what output come from their effort to understand diabetes and to overcome it.

 

 

 

INTRODUCTION:

Diabetes is generally considered as chronic disorder of metabolism that affects the insulin production capacity of body. Insulin is hormones that can convert food in to energy which is also called glucose or sugar, insulin is released from Beta cell of pancreas to transport glucose into cell. ^[1]T.DUSO et.,al Sep 2014. Diabetes may be occurring due to either less production of insulin by beta cell of pancreas or due to cell not responding to the existing insulin ^[2] Z. Tao et.,al Sep2015diabetes is associated with Serious long-term complications which include heart diseases, stroke, foot ulcer, eye damage, disease related to kidney^.[3] PA. Kumaret., al

 

Diabetes is mainly classified in three types:

Type1:

When the beta cell of pancreas is unable to produced sufficient amount of insulin which leads to insulin deficiency. Destruction of beta cell by auto immune attack by T cell is the primary cause of type1 diabetes it is also called insulin dependent diabetes mellitus^{. [4]}JF. Munni et., al

 

Type2:

When insulin produced by beta cell is resist by cell, it is also called non-insulin dependent diabetes mellitus in type 2 diabetes cells not responded to the insulin produced by beta cell. ^[5] J. Riserus et., al Jan 2009

 

Type3:

Gestational diabetes occurs when pregnant women developed high blood sugar level without previous history. ^[2] Z. Tao et., al Sep 2015

 

Pathophysiology of Diabetes Mellitus:

Type -1 diabetes:

The major factor responsible for type-1 diabetes is autoimmune attack by T-antigen result in destruction of beat cell, which in turn result in insulin deficiency and less production of insulin. Various factors are there which triggered the autoimmune destruction of beta cell, such as environmental factor, genetic factor. Type-1 diabetes is generally occurring before age of 30 years. Individual suffering from type -1 diabetes has to take insulin from outside of body because his/her body is no longer able to produce insulin.^[6] C. Archana et., al Type -1 diabetes also result in increase in ketone level because due to less insulin glucose could not enter into cell and thus remain into blood vessel ,due to which body fat is broken and release glycerol and free fatty acid through biolysis, this free fatty acid can be converted into ketone and which ultimately decrease concentration of hydrogen ion and also decrease level of electrolyte  thus cause dehydration and frequent urination which are common symptom of type -1  diabetes ,untreated ketoacidosis may result in death.^[7] MH. Dawood et.,al 2015

 

Type-2 diabetes:

Unlike type -1 diabetes which may be due to autoimmune attack of Antigen on beta cell type-2 diabetes is mainly caused due to desensitization of cell, that means beta cell can produce sufficient amount of insulin but due to cellular resistance insulin is not used by cell. ^[2] Z. Tao et., al Sep 2015 Type -2 diabetes is characterized by 3 disorder (1) excess glucose production by liver (2) dysfunction in production of insulin by pancreases (3) peripheral resistance of insulin.

 

Major factor for insulin resistance is obesity, about 80% of people who suffered from type -2 diabetes have obesity problem, and ketoacidosis is generally not seen in type -2 diabetes because there is enough production of insulin to prevent ketone formation. ^[2] Z. Tao et.,al Sep 2015

 

Fig-1: Various steps involved in the occurrence of Diabetes

 

Management of Diabetes:

Treatment of diabetes is based on consideration of following points

 

Prevention:

About 80-90% of diabetes patients are suffering from type -2 diabetes, which is associated with obesity and overweight. Physical activity, eating healthy diet like protein and fiber rich diet which include whole grain, green vegetable, consumption of this can reduce the risk of type -2 diabetes, moreover less consumption of sugar rich food and less use of tobacco, smoking can also reduce diabetes risk^.[8] HH. Kyu et., al^[9] N. Demasi et., al^[10] C. Willi et., al Dec.2007

 

Management:

Management of individual routine can be helpful in treatment of type -2 diabetes. Management of diet with less sugar consumption, involving in physical exercise and weight loss training should be recommended.^[11] R. Saglam Belen et. ,al Jan 2015^[12] N. Engl et., al Dec 2005^[13][14] PR. Cavanagh et., al May 2004.

Medication:

Use of several medicines or anti hyper glycemic agent can be helpful in overcoming diabetes. In type-1 diabetes insulin injection is the only option. Type-2 can be treated with some drugs. Metformin is the choice of drug for type-2 diabetes to control blood sugar level. 02^[5] J. Riserus et., al Jan 2009^[15]AJ. Krentz et., al Feb 2005^[16] J. Cheng et., al May 2014

 

Evaluation of Anti Diabetic Activity: 

Anti diabetic activity of any compound can be evaluated either by in vivo method or by in vitro techniques. In vivo method involve use of different experimental animal models while in vitro techniques can be use outside of body by using different cell line.

 

 

In vivo Methods:

Different animal models are used in evaluation of any compound. Rodents are generally used in diabetes evaluation like rat, mice. Rodents are given with different chemicals to induce diabetes, and then the animals are treated with test compound. Experiment is performed in groups of animals (Test group, treated group and controlled group etc.).^[17] TS. Roopashree et., al Sep 2008 ^[18] BV. Ghule et., al Nov 2006

 

In-vitro techniques:

In vitro methods involve use of cell line techniques either obtained from mouse Insulinoma or from human beta cell for the evaluation of diabetes. Cell lines are basically the cell culture technique which is obtained from subculture of primary cell culture. Cell lines are sometime immortalized by inducing some carcinogenic mutation to the normal cell line.^[17] TS. Roopashree et., al Sep 2008 ^[18] BV. Ghule et., al Nov 2006

 

Table :( 1) List of Animal models and Cell lines

 

 

 

Table: (2) List of Phytoconstituentsact as Anti-diabetic Agent

S.N.	SINTIFIC NAME/FAMILY	PHYTOCONSTITUENT	ACTIVITY	MECHANISM
1.	Acorus calamus (Acoraceae)	Phenylpropanoids, Sesquiterpenes, Flavones, Triterpenoid andsaponins	Ant diabetics	Decrease the activity of glucose-6 phosphate and fructose 1, 6phosphatases enzyme.
2.	Adina cordifolia (Rubiaceae)	Tannins, Saponins, and Flavonoids.	Ant diabetics	Increase the insulin secretion or inhibit the intestine absorption of glucose.
3.	Syzygium cumini (myrtaceae)	GlycosideJjamboline, Natural acid, Kaemferol, Myrecetin, Tannins.	Ant diabetics	Myricetin has been shown to improved GLUT-4express in both adipose tissue and skeletal muscles, Methanolic extract increase mRNA expression glucose transporter (GLUT-4)
4.	Andrographis paniculatanees  / Kalmegh (Acanthaceae)	Ditereneclactones, flavonoids.	Ant diabetics	A significant decrease in blood glucose level, hipoglysemic activity of Andrographis paniculata was reported.
				Inhibition
5.	Camellia sinensis (Theaceae)	Caffeine and catechism.	Ant diabetics	Development of insulin resistance hypoglymia and other metabolic effect also decease glucose absorption from intestine.
6.	Momoradic charantia/ Karela (Cucurbitaceae)	Triterpene, steroid, alkaloid. Inorganic, lipid, and phenolic compound.	Ant diabetics	It decreases glucose oxidation and glucose uptake in liver decrease gluconeogenesis it also promotes lipid metabolism and fat reduction.

 

 

 

Table :( 3) List of past inventions using different Cell lines^[19],PM. Dean et.,al July 1968 ^[20] AF. Gazdar et.,al Jan 1980 ^[21]A. Merglene et., al Feb 2004 ^[22] CB. Nwegard et., al Mar 1994

S.no.	Name of Scientists	Years	Title of work	Output
1.	Dean and Matthews	1968	Electrical activity of beta cell	This research give idea about the electrical condicity of cell, as a result insulin secreation is increase due to due to cyctoplasmicincrease in Calcium concentration.
2.	Gazdar and Santerre	1980, 1981	Immortalisation of beta cell	Beta cell can be immortalized by induction of tumor to pancreatic cell by irradiation or by virus, immortalized beta cellHave tendency to proliferate infinite time and thus in turn increase insulin secretion.
3.	Merglen	2004	Isolated clonal INS1E cells from the parenteral cells.	These cells display stable differentiated beta cell phenotype over 116 passages and are able to secrete insulin in response to elevated glucose concentrations. Their concentration-dependence curve is similar to that of rat islets.
4.	Newgard,	1994	Insulin-secreting cells of non-islet cell origin	Stable transfection of AtT-20 cells with a construct in which a viral promoter was used to direct expression of the human proinsulincDNA resulted in cell lines which secreted fully processed insulin. EAtT-20 cell line was engineered from ACTHsecreting cells of the anterior pituitary.

 

CONCLUSION:

Diabetes is a chronic metabolic disorder which is characterized by rise in blood glucose level, type 1 diabetes is due to low insulin secretion and type 2 diabetes is caused due to cell not responsive to the insulin. Prevention, management and proper treatment can reduce the risk of diabetes. Large number of herbs has been found to have ant diabetes property, phytochemical constituent of different plant can be evaluated for their ant diabetic property, they can either decrease glucose -6 phosphate activity or increase insulin secretion. Recent advancement in past few years in different pancreatic beta cell line provided the better understanding of the insulin secretion and thus promotes the treatment. in vivo models including different experimental animal and investor methods by use of different cell line derived either from mouse insulinoma or from human pancreatic cell. All this techniques provide the base for understanding the mechanism of diabetes and evaluation of ant diabetic activity and thus help to cure or overcome these diseases.

 

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