CNS mechanisms that regulate glucose homeostasis in health and disease

 

The primary focus of our Laboratory is to examine the CNS mechanisms involved in the maintenance of glucose homeostasis and how they are impacted on, or contribute to the development of disease states such as diabetes. Glucose homeostasis is abnormal in all forms of diabetes, reflecting abnormalities in both insulin secretion and insulin sensitivity. These leads to marked fluctuations in blood glucose levels as illustrated in the Figures below:

Glucose profile in Individual with Type 1 DiabetesGlucose Profile in Non-Diabetic Individual

A major research area for our laboratory is in those mechanisms underlying the detection of hypoglycaemia in diabetes and why they fail over time. In Type 1 Diabetes, severe hypoglycaemia is the major metabolic side-effect of insulin therapy and has emerged as the “…major limiting factor to optimal glycaemic management in Type 1 Diabetes” (Cryer PE, Banting Lecture to American Diabetes Association, 1994). Severe hypoglycaemia in T1DM results from two primary abnormalities. The first reflects the limitations of current insulin delivery systems that results in raised systemic insulin levels, because of the inability to deliver insulin directly to the portal system (insulin is ~50% metabolized in the liver), as well as the inability to switch-off insulin delivery during hypoglycaemia. The second is because of widespread defects in the normal hormonal counterregulatory response to hypoglycaemia, reducing an individual’s ability to respond to and counteract the glucose lowering action of insulin. The brain plays a major role in the detection of hypoglycaemia. Specialized glucose-sensing neurons can be found in a number of brain regions such as the ventromedial hypothalamus and medial amygdalar nucleus. Key components of this sensing mechanism include glucokinase, AMP-activated protein kinase, the ATP-sensitive potassium channel and the inhibitory neurotransmitter GABA. Our laboratory uses a number of techniques in order to examine the mechanisms and neural circuitry of hypoglycaemia. These include; (i) the study of hypothalamic glucose-sensing cell lines (ii) in vivo metabolic phenotyping and study of transgenic mice (iii) in vivo study of rats using pharmacological or viral vector-driven manipulation of discrete brain regions and neural tracing studies. In addition, we also have an interest in examining how these brain regions contribute to energy metabolism and to the development of type 2 diabetes through the regulation of hepatic glucose production and pancreatic beta-cell insulin secretion.

 

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Guidelines for Treating Lows by Age

children v. diabetes

Guidelines for

Treating Lows by Age

When treating hypoglycemia, the following table will help you determine how much sugar to use.

Source of Sugar
Under 6 Years of Age

•   (5 -10 grams)

6-10 Years of

Age (10-15 grams)

Over 10 Years of

Age (15-20 grams)

Glucose Tablets (large)

(1 tablet = 5 grams)

1 – 2 tablets 2 – 3 tablets 3 – 4 tablets
Glucose Tablets (small)

(1 tablet = 4 grams)

1 – 2 tablets 3 – 4 tablets 4 – 5 tablets
Glucose gel

(31 gram tube)

1/6-1/3 tube 1/3-1/2 tube 1/2 – 2/3 tube
Cake icing (small tube)

(1 teaspoon = 4 grams)

2 teaspoons 3 teaspoons 4 – 5 teaspoons
Honey, maple, or Karo Syrup

(1 teaspoon = 5 grams)

1 – 2 teaspoons 2 – 3 teaspoons 3 – 4 teaspoons
Orange juice

(1/3 cup = 10 grams)

1/4 -1/2 cup 1/2 – 3/4 cup 3/4 -1 cup
Apple juice

(1/3 cup = 10 grams)

1/4 -1/2 cup 1/2 – 3/4 cup 3/4 -1 cup
Table sugar

(1 teaspoon = 4 grams)

2 teaspoons 3 teaspoons 4 – 5 teaspoons
Regular soda pop

(1 ounce = 3 grams)

2-3 ounces 4-5 ounces 5-6 ounces
Raisins

(1 tbsp = 7 1/2 grams)

1 tablespoon 1 1/2-2 tablespoons 2 1/2-3 tablespoons
Lifesavers

(1=3 grams)

2-3 4-5 5-7
Milk 2%

(8 ounces = 12 grams)

4-5 ounces 6-7 ounces 8-10 ounces

Reference: Understanding Insulin-Dependent Diabetes, 9th Edition, by Dr. Peter Chase, page 23.

Nocturnal hypoglycemia

Voglibose administration before the evening meal improves nocturnal hypoglycemia in insulin-dependent diabetic patients with intensive insulin therapy

Taira M, Takasu N, Komiya I, Taira T, Tanaka H.

Second Department of Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

Nocturnal hypoglycemia is one of the serious complications of intensive insulin therapy in patients with insulin-dependent diabetes mellitus (IDDM; type 1 DM). We assessed the effect of voglibose (alpha-glucosidase inhibitor) administration before the evening meal on nocturnal hypoglycemia in IDDM patients with intensive insulin therapy. Ten IDDM patients received 0.3 mg voglibose just before the evening meal for 5 days. The diet and insulin regimen were not changed throughout the study. Nocturnal plasma glucose levels (10 PM, 3 AM, and 7 AM) were studied in these patients before and during voglibose administration. Blood glucose levels were measured at 3 AM before and during voglibose treatment. The mean plasma glucose level at 3 AM was 3.4+/-0.4 mmol/L before voglibose treatment and 7.3+/-1.0 mmol/L during treatment. Plasma glucose at 3 AM was elevated in 9 of 10 patients with voglibose. The decrease in plasma glucose from 10 PM to 3 AM was 6.5+/-0.8 mmol/L before voglibose administration but 3.2+/-0.9 mmol/L during treatment (P < .01). The hypoglycemia rate was 52% (17 of 33 nights) before voglibose administration but only 9.1% (3 of 33 nights) during treatment. We conclude that voglibose administration before the evening meal improves nocturnal hypoglycemia in IDDM patients with intensive insulin therapy.