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Anti-diabetic Agents Florencia D. Munsayac, MD, FPSECP, MBA, RMT
 
The Endocrine Pancreas 1 million islets of Langerhans ,[object Object],[object Object],[object Object],[object Object],[object Object]
Diabetes Mellitus ,[object Object],[object Object],[object Object],[object Object],Type 2 Diabetes - blood glucose levels rise due to  1) Lack of insulin production 2) Insufficient insulin action (resistant cells) - commonly detected after 40 - eventually leads to β-cell failure  (resulting in insulin dependence) ,[object Object],[object Object],[object Object],Type 4 Diabetes (Gestational Diabetes)   3-5% of pregnant women in the US develop gestational diabetes
Diabetes Mellitus ,[object Object],[object Object],[object Object],[object Object]
Diabetes – Insulin (synthesis, storage, secretion) This light micrograph of a section of the human pancreas shows one of the islets of Langerhans,  center,  a group of modified glandular cells. These cells secrete insulin, a hormone that helps the body metabolize sugars, fats, and starches. The blue and white lines in the islets of Langerhans are blood vessels that carry the insulin to the rest of the body.
Diabetes – Insulin (synthesis, storage, secretion) Insulin  is a small protein consisting of an  A  chain of 21 amino acids linked by two disulfide (S—S) bridges to a   B  chain of 30 amino acids. Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose .
Diabetes – Insulin (synthesis, storage, secretion) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Diabetes – Insulin (synthesis, storage, secretion)
Diabetes – Insulin (synthesis, storage, secretion) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Diabetes – Insulin ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Diabetes – Insulin (Biochemical Role) ,[object Object],[object Object],[object Object],[object Object]
Effects of Insulin on its Targets ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],protein synthesis amino acids u ptake glucose uptake glycogen  synthesis enzyme production glycogen breaking fat  synthesis
Effects of Insulin on its Targets Transporters Tissues GlucoseKm (Mmo/L)  Function GLUT 1 All tissues, esp.red cells, brain 1-2 Basal uptake of glucose; Transport across the BBB GLUT 2 B cells of pancreas; Liver; kidney; gut 15-20  Regulation of insulin release, other aspects of glucose homeostasis GLUT 3 Brain, kidney, placenta, other tissues < 1 Uptake into neurons, other tissues GLUT 4 Muscle, adipose 5 Insulin-mediated uptake of glucose GLUT 5 Gut, kidney  1-2 Absorption of fructose
Diabetes - Insulin Receptor ,[object Object],[object Object]
Principal Types and Duration of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Principal Types and Duration of Action ,[object Object],6-7 hrs 2 hrs 10-20 min HIRI 3-5 hrs 1hr 5-15 min Insulin glulysine 3-5 hrs 1 hr 5-15 min Insulin aspart 3-5 hrs 1 hr 5-15 min Insulin lispro Duration Peak Onset Rapid-acting insulin
Principal Types and Duration of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Principal Types and Duration of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Principal Types and Duration of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Principal Types and Duration of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Species of Insulin ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Delivery Systems   A.   Portable Pen Injectors - to facilitate multiple SQ injections    B. Continuous Subcutaneous Insulin Infusion Devices (CSII, Insulin Pumps) - encouraged for individuals who are unable to obtain target control  while on multiple injection regimens & where excellent glycemic control is desired, such as during pregnancy - velosulin (reg. insulin) & insulin aspart and lispro   C.   Inhaled Insulin - have a rapid route and a relatively short duration of  action - used to cover mealtime insulin requirements  - to correct high glucose levels  
Factors that Affect Insulin Absorption: -      site of injection: abdomen, buttock, anterior thigh, or dorsal  arm -      type of insulin -      subcutaneous blood flow: massage, hot baths, or exercise -      smoking -      regional muscular activity at the site of the injection -      volume & concentration of injected insulin -      depth of injection  
Complications of Insulin Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Complications of Insulin Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Insulin Secretagogues: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Biguanides ,[object Object],[object Object],[object Object],[object Object],[object Object]
Biguanides ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Biguanides ,[object Object],[object Object],[object Object],[object Object]
Biguanides ,[object Object],[object Object],[object Object]
Biguanides ,[object Object],[object Object],[object Object],[object Object]
Thiazolidinediones ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thiazolidinediones ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thiazolidinediones ,[object Object],[object Object],[object Object],[object Object]
Thiazolidinediones ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thiazolidinediones ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Alpha-Glucosidase Inhibitors ,[object Object],[object Object],[object Object]
Alpha-Glucosidase Inhibitors ,[object Object],[object Object],[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   ,[object Object],[object Object]
Pathophysiology of Type 2 Diabetes Insulin Resistance ,[object Object],[object Object]
Pathophysiology of Type 2 Diabetes  Beta cell defect ,[object Object],[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   Other Factors ,[object Object],[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   The Glucagon Factor ,[object Object],[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   The Glucagon Factor ,[object Object],[object Object],[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   The Gastric Emptying Factor ,[object Object],[object Object]
Pathophysiology of Type 2 Diabetes   One last observation ,[object Object],[object Object],[object Object],[object Object]
What are incretins? ,[object Object],[object Object],[object Object]
What are incretins? Gastric Inhibitory Polypeptide (GIP)   ,[object Object]
What are incretins?   Glucagon-like peptide-1 (GLP-1)   ,[object Object],[object Object],[object Object]
Actions of GLP-1 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Actions of GLP-1 ,[object Object],[object Object],[object Object],[object Object]
Actions of GLP-1 ,[object Object]
Actions of GLP-1   The Problem ,[object Object]
The Solution ,[object Object],[object Object],[object Object]
Incretin mimetics Exenatide   ,[object Object],[object Object],[object Object],[object Object]
 
Incretin mimetics Exenatide ,[object Object],[object Object],[object Object],[object Object]
 
Weight Loss With Exenatide   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Nausea With Exenatide   ,[object Object],[object Object]
Incretin mimetics   Recent Advances ,[object Object],[object Object]
Dipeptidyl Peptidase-IV Antagonists   ,[object Object],[object Object],[object Object],[object Object],[object Object]
Dipeptidyl Peptidase-IV Antagonists   Sitagliptin and Vildagliptin ,[object Object],[object Object],[object Object],[object Object]
Dipeptidyl Peptidase-IV Antagonists   Recent Advances ,[object Object],[object Object]
Newer Agent ,[object Object],[object Object],[object Object],[object Object],[object Object]
Newer Agent ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object]
Summary ,[object Object],[object Object],[object Object]
Summary ,[object Object],[object Object],[object Object],[object Object]
THANK YOU
Insulin Drug Evolution ,[object Object],[object Object]
Insulin Drug Evolution ,[object Object],Recombinant DNA technology has also made it   possible   to manufacture slightly-modified forms of human insulin   that work faster (Humalog® and NovoLog®) or slower   (Lantus®) than regular human insulin.
 

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Antidiabetic agents1dated

  • 1. Anti-diabetic Agents Florencia D. Munsayac, MD, FPSECP, MBA, RMT
  • 2.  
  • 3.
  • 4.
  • 5.
  • 6. Diabetes – Insulin (synthesis, storage, secretion) This light micrograph of a section of the human pancreas shows one of the islets of Langerhans, center, a group of modified glandular cells. These cells secrete insulin, a hormone that helps the body metabolize sugars, fats, and starches. The blue and white lines in the islets of Langerhans are blood vessels that carry the insulin to the rest of the body.
  • 7. Diabetes – Insulin (synthesis, storage, secretion) Insulin is a small protein consisting of an A chain of 21 amino acids linked by two disulfide (S—S) bridges to a B chain of 30 amino acids. Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose .
  • 8.
  • 9. Diabetes – Insulin (synthesis, storage, secretion)
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. Effects of Insulin on its Targets Transporters Tissues GlucoseKm (Mmo/L) Function GLUT 1 All tissues, esp.red cells, brain 1-2 Basal uptake of glucose; Transport across the BBB GLUT 2 B cells of pancreas; Liver; kidney; gut 15-20 Regulation of insulin release, other aspects of glucose homeostasis GLUT 3 Brain, kidney, placenta, other tissues < 1 Uptake into neurons, other tissues GLUT 4 Muscle, adipose 5 Insulin-mediated uptake of glucose GLUT 5 Gut, kidney 1-2 Absorption of fructose
  • 15.
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22.  
  • 23.
  • 24.
  • 25. Insulin Delivery Systems   A.  Portable Pen Injectors - to facilitate multiple SQ injections   B. Continuous Subcutaneous Insulin Infusion Devices (CSII, Insulin Pumps) - encouraged for individuals who are unable to obtain target control while on multiple injection regimens & where excellent glycemic control is desired, such as during pregnancy - velosulin (reg. insulin) & insulin aspart and lispro   C.   Inhaled Insulin - have a rapid route and a relatively short duration of action - used to cover mealtime insulin requirements - to correct high glucose levels  
  • 26. Factors that Affect Insulin Absorption: -      site of injection: abdomen, buttock, anterior thigh, or dorsal arm -      type of insulin -      subcutaneous blood flow: massage, hot baths, or exercise -      smoking -      regional muscular activity at the site of the injection -      volume & concentration of injected insulin -      depth of injection  
  • 27.
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
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Editor's Notes

  1. Thank you…